TP53 Regulates Transcription of Cell Cycle Genes (Homo sapiens)

From WikiPathways

Revision as of 13:37, 16 August 2017 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
1, 3, 6, 11-14, 18...66, 12044, 895213, 94, 1184674, 8667, 1051318, 7759, 8018, 23, 44, 77, 8969, 1193, 12, 25, 36, 711418, 7769, 1195114596, 107411161209858, 74, 861, 43, 52, 934134, 99, 105, 11123, 44, 1036, 107, 1163910411, 10746, 5720, 44, 8923, 29, 44, 56, 77...511067, 11, 1071044870cytosolnucleoplasmMitotic G1-G1/SphasesCARM1E2F7PCNA p-S15,S20-TP53 TNKS1BP1 E2F7,E2F8dimers:E2F1 GeneGADD45A:PCNAARID3A Genep-S15,S20-TP53Tetramer:PLAGL1GenePLK2 Gene CCNB1 TFDP2 CNOT10 BTG2 Genep-S4-NPM1CDC25C GeneNPM1BAXCNOT7 E2F7 Gene E2F8CDKN1A mRNA E2F7:E2F8CNOT11 SFNp-S15,S20-TP53 PCBP4RBL1 CCNE2 CCNE:CDK2CNOT1 p-S15,S20-TP53:EP300:PRMT1:CARM1:GADD45A GeneCCNA1 CNOT7 CDKN1A mRNACCNE1 BTG2AURKABTG2:CCR4-NOTE2F7 RGCC Genep-S15,S20-TP53Tetramer:ZNF385A:SFN GeneCCNE1 Intrinsic Pathwayfor Apoptosisp-S15,S20-TP53Tetramer:RGCC GeneCNOT8 p-S15,S20-TP53Tetramer:ZNF385ACENPJp-S15,S20-TP53 CNOT6 PCBP4 GeneTNKS1BP1 Mitotic G2-G2/MphasesZNF385A BTG2 Gene ATPGADD45A ZNF385A BTG2 p-S15,S20-TP53 E2F7 p-S15,S20-TP53 RQCD1 p-S15,S20-TP53 p-S191-CDC25CZNF385A E2F8 p-S15,S20-TP53Tetramer:PCBP4 GenePLAGL1E2F1 geneCCNA1 p-S15,S20-TP53 SFN p-S15,S20-TP53Tetramer:E2F4:(TFDP1,TFDP2):(RBL1,RBL2):CDC25C GeneSFN Dimer:CCNB1:CDK1PCBP4:CDKN1A mRNAGADD45A Gene p-S15,S20-TP53TetramerCDKN1AE2F8 CDKN1A,CDKN1BCNOT6L E2F7 homodimerCyclinE:CDK2:CDKN1A,CDKN1BTFDP1 RBL1 EP300 CNOT2 CDKN1A geneGADD45A:AURKAp-S15,S20-TP53 p-S15,S20-TP53Tetramer:PLK3 GeneEP300Regulation of TP53Activityp-S15,S20-TP53 E2F8 homodimerCNOT8 CDK2 TFDP2 AURKA p-S15,S20-TP53Tetramer:E2F7 GeneGADD45A SFN CCNB1:CDK1CDKN1B p-S15,S20-TP53 CDK2 CNOT6L RGCCCCNA2 PCNA CDKN1A CDKN1A CNOT4 CDK2 p-S15,S20-TP53 ADPCDC25C Gene PCNA homotrimerp-S15,S20-TP53Tetramer:BTG2 GeneRBL2 CNOT10 ATPPLK3 Gene CARM1 RQCD1 E2F8 ARID3APRMT1E2F7 p-S15,S20-TP53 CNOT1 p-S15,S20-TP53 CNOT6 CCNB1 CyclinA:Cdk2:p21/p27complexPLK2 GeneE2F7 GeneE2F4 p-S589,S595-CENPJPLK3Deadenylation-dependent mRNA decayRBL2 SFN DimerPLAGL1 GeneCDKN1B E2F4 E2F1BAX CNOT2 SFN PRMT1 CDK1 CCNA:CDK2SFN Gene CDKN1A PLK3 GeneCNOT3 E2F7 p-S15,S20-TP53Tetramer:ARID3AGeneCCNE2 GADD45AADPPLAGL1 Gene TP53 RegulatesTranscription ofCell Death GenesTFDP1 PCBP4 E2F8 SFN Dimer:BAXCDC25CCDK2 CCR4-NOT ComplexPLK2PCBP4 Gene CNOT3 CDK1 SFN GeneARID3A Gene p-S15,S20-TP53 RGCC Gene E2F7,E2F8 dimersE2F1 gene p-S15,S20-TP53Tetramer:ZNF385A:CDKN1A GeneCCNA2 CNOT4 p-S15,S20-TP53Tetramer:PLK2 GeneE2F4:(TFDP1,TFDP2):(RBL1,RBL2)CNOT11 GADD45A GeneCDKN1A gene CDKN1B 1072, 8, 14-16, 19...1075121, 42, 9614595, 9, 837723, 10322, 7839104441207069, 11934, 99, 1054610, 17, 24, 33, 45...1318, 774, 73, 110, 11767, 10511641


Under a variety of stress conditions, TP53 (p53), stabilized by stress-induced phosphorylation at least on S15 and S20 serine residues, can induce the transcription of genes involved in cell cycle arrest. Cell cycle arrest provides cells an opportunity to repair the damage before division, thus preventing the transmission of genetic errors to daughter cells. In addition, it allows cells to attempt a recovery from the damage and survive, preventing premature cell death.

TP53 controls transcription of genes involved in both G1 and G2 cell cycle arrest. The most prominent TP53 target involved in G1 arrest is the inhibitor of cyclin-dependent kinases CDKN1A (p21). CDKN1A is one of the earliest genes induced by TP53 (El-Deiry et al. 1993). CDKN1A binds and inactivates CDK2 in complex with cyclin A (CCNA) or E (CCNE), thus preventing G1/S transition (Harper et al. 1993). Nevertheless, under prolonged stress, the cell destiny may be diverted towards an apoptotic outcome. For instance, in case of an irreversible damage, TP53 can induce transcription of an RNA binding protein PCBP4, which can bind and destabilize CDKN1A mRNA, thus alleviating G1 arrest and directing the affected cell towards G2 arrest and, possibly, apoptosis (Zhu and Chen 2000, Scoumanne et al. 2011). Expression of E2F7 is directly induced by TP53. E2F7 contributes to G1 cell cycle arrest by repressing transcription of E2F1, a transcription factor that promotes expression of many genes needed for G1/S transition (Aksoy et al. 2012, Carvajal et al. 2012). ARID3A is a direct transcriptional target of TP53 (Ma et al. 2003) that may promote G1 arrest by cooperating with TP53 in induction of CDKN1A transcription (Lestari et al. 2012). However, ARID3A may also promote G1/S transition by stimulating transcriptional activity of E2F1 (Suzuki et al. 1998, Peeper et al. 2002).<p>TP53 contributes to the establishment of G2 arrest by inducing transcription of GADD45A and SFN, and by inhibiting transcription of CDC25C. TP53 induces GADD45A transcription in cooperation with chromatin modifying enzymes EP300, PRMT1 and CARM1 (An et al. 2004). GADD45A binds Aurora kinase A (AURKA), inhibiting its catalytic activity and preventing AURKA-mediated G2/M transition (Shao et al. 2006, Sanchez et al. 2010). GADD45A also forms a complex with PCNA. PCNA is involved in both normal and repair DNA synthesis. The effect of GADD45 interaction with PCNA, if any, on S phase progression, G2 arrest and DNA repair is not known (Smith et al. 1994, Hall et al. 1995, Sanchez et al. 2010, Kim et al. 2013). SFN (14-3-3-sigma) is induced by TP53 (Hermeking et al. 1997) and contributes to G2 arrest by binding to the complex of CDK1 and CCNB1 (cyclin B1) and preventing its translocation to the nucleus. Phosphorylation of a number of nuclear proteins by the complex of CDK1 and CCNB1 is needed for G2/M transition (Chan et al. 1999). While promoting G2 arrest, SFN can simultaneously inhibit apoptosis by binding to BAX and preventing its translocation to mitochondria, a step involved in cytochrome C release (Samuel et al. 2001). TP53 binds the promoter of the CDC25C gene in cooperation with the transcriptional repressor E2F4 and represses CDC25C transcription, thus maintaining G2 arrest (St Clair et al. 2004, Benson et al. 2014).<p>Several direct transcriptional targets of TP53 are involved in cell cycle arrest but their mechanism of action is still unknown. BTG2 is induced by TP53, leading to cessation of cellular proliferation (Rouault et al. 1996, Duriez et al. 2002). BTG2 binds to the CCR4-NOT complex and promotes mRNA deadenylation activity of this complex. Interaction between BTG2 and CCR4-NOT is needed for the antiproliferative activity of BTG2, but the underlying mechanism has not been elucidated (Rouault et al. 1998, Mauxion et al. 2008, Horiuchi et al. 2009, Doidge et al. 2012, Ezzeddine et al. 2012). Two polo-like kinases, PLK2 and PLK3, are direct transcriptional targets of TP53. TP53-mediated induction of PLK2 may be important for prevention of mitotic catastrophe after spindle damage (Burns et al. 2003). PLK2 is involved in the regulation of centrosome duplication through phosphorylation of centrosome-related proteins CENPJ (Chang et al. 2010) and NPM1 (Krause and Hoffmann 2010). PLK2 is frequently transcriptionally silenced through promoter methylation in B-cell malignancies (Syed et al. 2006). Induction of PLK3 transcription by TP53 (Jen and Cheung 2005) may be important for coordination of M phase events through PLK3-mediated nuclear accumulation of CDC25C (Bahassi et al. 2004). RGCC is induced by TP53 and implicated in cell cycle regulation, possibly through its association with PLK1 (Saigusa et al. 2007). PLAGL1 (ZAC1) is a zinc finger protein directly transcriptionally induced by TP53 (Rozenfeld-Granot et al. 2002). PLAGL1 expression is frequently lost in cancer (Varrault et al. 1998) and PLAGL1 has been implicated in both cell cycle arrest and apoptosis (Spengler et al. 1997), but its mechanism of action remains unknown.<p>The zinc finger transcription factor ZNF385A (HZF) is a direct transcriptional target of TP53 that can form a complex with TP53 and facilitate TP53-mediated induction of CDKN1A and SFN (14-3-3 sigma) transcription (Das et al. 2007).<p>For a review of the role of TP53 in cell cycle arrest and cell cycle transcriptional targets of TP53, please refer to Riley et al. 2008, Murray-Zmijewski et al. 2008, Bieging et al. 2014, Kruiswijk et al. 2015. View original pathway at:Reactome.</div>


Pathway is converted from Reactome ID: 6791312
Reactome version: 61
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

Quality Tags

Ontology Terms



View all...
  1. Ma K, Araki K, Ichwan SJ, Suganuma T, Tamamori-Adachi M, Ikeda MA.; ''E2FBP1/DRIL1, an AT-rich interaction domain-family transcription factor, is regulated by p53.''; PubMed Europe PMC Scholia
  2. Lestari W, Ichwan SJ, Otsu M, Yamada S, Iseki S, Shimizu S, Ikeda MA.; ''Cooperation between ARID3A and p53 in the transcriptional activation of p21WAF1 in response to DNA damage.''; PubMed Europe PMC Scholia
  3. Depoortere F, Van Keymeulen A, Lukas J, Costagliola S, Bartkova J, Dumont JE, Bartek J, Roger PP, Dremier S.; ''A requirement for cyclin D3-cyclin-dependent kinase (cdk)-4 assembly in the cyclic adenosine monophosphate-dependent proliferation of thyrocytes.''; PubMed Europe PMC Scholia
  4. Salvesen GS, Duckett CS.; ''IAP proteins: blocking the road to death's door.''; PubMed Europe PMC Scholia
  5. Thurlings I, Martínez-López LM, Westendorp B, Zijp M, Kuiper R, Tooten P, Kent LN, Leone G, Vos HJ, Burgering B, de Bruin A.; ''Synergistic functions of E2F7 and E2F8 are critical to suppress stress-induced skin cancer.''; PubMed Europe PMC Scholia
  6. Zalmas LP, Zhao X, Graham AL, Fisher R, Reilly C, Coutts AS, La Thangue NB.; ''DNA-damage response control of E2F7 and E2F8.''; PubMed Europe PMC Scholia
  7. Guan B, Yue P, Clayman GL, Sun SY.; ''Evidence that the death receptor DR4 is a DNA damage-inducible, p53-regulated gene.''; PubMed Europe PMC Scholia
  8. Sax JK, Fei P, Murphy ME, Bernhard E, Korsmeyer SJ, El-Deiry WS.; ''BID regulation by p53 contributes to chemosensitivity.''; PubMed Europe PMC Scholia
  9. Bieging KT, Mello SS, Attardi LD.; ''Unravelling mechanisms of p53-mediated tumour suppression.''; PubMed Europe PMC Scholia
  10. Mauxion F, Faux C, Séraphin B.; ''The BTG2 protein is a general activator of mRNA deadenylation.''; PubMed Europe PMC Scholia
  11. Buckbinder L, Talbott R, Velasco-Miguel S, Takenaka I, Faha B, Seizinger BR, Kley N.; ''Induction of the growth inhibitor IGF-binding protein 3 by p53.''; PubMed Europe PMC Scholia
  12. Ruiz de Almodóvar C, Ruiz-Ruiz C, Rodríguez A, Ortiz-Ferrón G, Redondo JM, López-Rivas A.; ''Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor TRAIL-R3 is up-regulated by p53 in breast tumor cells through a mechanism involving an intronic p53-binding site.''; PubMed Europe PMC Scholia
  13. Passer BJ, Nancy-Portebois V, Amzallag N, Prieur S, Cans C, Roborel de Climens A, Fiucci G, Bouvard V, Tuynder M, Susini L, Morchoisne S, Crible V, Lespagnol A, Dausset J, Oren M, Amson R, Telerman A.; ''The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase.''; PubMed Europe PMC Scholia
  14. Phan RT, Dalla-Favera R.; ''The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.''; PubMed Europe PMC Scholia
  15. Wu GS, Burns TF, McDonald ER, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS.; ''KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene.''; PubMed Europe PMC Scholia
  16. Montagnoli A, Fiore F, Eytan E, Carrano AC, Draetta GF, Hershko A, Pagano M.; ''Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.''; PubMed Europe PMC Scholia
  17. Rozenfeld-Granot G, Krishnamurthy J, Kannan K, Toren A, Amariglio N, Givol D, Rechavi G.; ''A positive feedback mechanism in the transcriptional activation of Apaf-1 by p53 and the coactivator Zac-1.''; PubMed Europe PMC Scholia
  18. Fritz DT, Bergman N, Kilpatrick WJ, Wilusz CJ, Wilusz J.; ''Messenger RNA decay in mammalian cells: the exonuclease perspective.''; PubMed Europe PMC Scholia
  19. Fosbrink M, Cudrici C, Niculescu F, Badea TC, David S, Shamsuddin A, Shin ML, Rus H.; ''Overexpression of RGC-32 in colon cancer and other tumors.''; PubMed Europe PMC Scholia
  20. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P.; ''Toxic proteins released from mitochondria in cell death.''; PubMed Europe PMC Scholia
  21. Suzuki M, Okuyama S, Okamoto S, Shirasuna K, Nakajima T, Hachiya T, Nojima H, Sekiya S, Oda K.; ''A novel E2F binding protein with Myc-type HLH motif stimulates E2F-dependent transcription by forming a heterodimer.''; PubMed Europe PMC Scholia
  22. Lau NC, Kolkman A, van Schaik FM, Mulder KW, Pijnappel WW, Heck AJ, Timmers HT.; ''Human Ccr4-Not complexes contain variable deadenylase subunits.''; PubMed Europe PMC Scholia
  23. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B.; ''WAF1, a potential mediator of p53 tumor suppression.''; PubMed Europe PMC Scholia
  24. Peeper DS, Shvarts A, Brummelkamp T, Douma S, Koh EY, Daley GQ, Bernards R.; ''A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence.''; PubMed Europe PMC Scholia
  25. Saito M, Novak U, Piovan E, Basso K, Sumazin P, Schneider C, Crespo M, Shen Q, Bhagat G, Califano A, Chadburn A, Pasqualucci L, Dalla-Favera R.; ''BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma.''; PubMed Europe PMC Scholia
  26. Spengler D, Villalba M, Hoffmann A, Pantaloni C, Houssami S, Bockaert J, Journot L.; ''Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain.''; PubMed Europe PMC Scholia
  27. Margalit O, Amram H, Amariglio N, Simon AJ, Shaklai S, Granot G, Minsky N, Shimoni A, Harmelin A, Givol D, Shohat M, Oren M, Rechavi G.; ''BCL6 is regulated by p53 through a response element frequently disrupted in B-cell non-Hodgkin lymphoma.''; PubMed Europe PMC Scholia
  28. Benson EK, Mungamuri SK, Attie O, Kracikova M, Sachidanandam R, Manfredi JJ, Aaronson SA.; ''p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexes.''; PubMed Europe PMC Scholia
  29. Ezzeddine N, Chen CY, Shyu AB.; ''Evidence providing new insights into TOB-promoted deadenylation and supporting a link between TOB's deadenylation-enhancing and antiproliferative activities.''; PubMed Europe PMC Scholia
  30. Das S, Raj L, Zhao B, Kimura Y, Bernstein A, Aaronson SA, Lee SW.; ''Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation.''; PubMed Europe PMC Scholia
  31. Liu X, Yue P, Khuri FR, Sun SY.; ''Decoy receptor 2 (DcR2) is a p53 target gene and regulates chemosensitivity.''; PubMed Europe PMC Scholia
  32. Rikhof B, Corn PG, El-Deiry WS.; ''Caspase 10 levels are increased following DNA damage in a p53-dependent manner.''; PubMed Europe PMC Scholia
  33. Wang W, Nacusi L, Sheaff RJ, Liu X.; ''Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection.''; PubMed Europe PMC Scholia
  34. Samuel T, Weber HO, Rauch P, Verdoodt B, Eppel JT, McShea A, Hermeking H, Funk JO.; ''The G2/M regulator 14-3-3sigma prevents apoptosis through sequestration of Bax.''; PubMed Europe PMC Scholia
  35. Burns TF, Fei P, Scata KA, Dicker DT, El-Deiry WS.; ''Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells.''; PubMed Europe PMC Scholia
  36. Zhang H.; ''Life without kinase: cyclin E promotes DNA replication licensing and beyond.''; PubMed Europe PMC Scholia
  37. Verdoodt B, Benzinger A, Popowicz GM, Holak TA, Hermeking H.; ''Characterization of 14-3-3sigma dimerization determinants: requirement of homodimerization for inhibition of cell proliferation.''; PubMed Europe PMC Scholia
  38. Logan N, Delavaine L, Graham A, Reilly C, Wilson J, Brummelkamp TR, Hijmans EM, Bernards R, La Thangue NB.; ''E2F-7: a distinctive E2F family member with an unusual organization of DNA-binding domains.''; PubMed Europe PMC Scholia
  39. Hiebert SW.; ''Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression.''; PubMed Europe PMC Scholia
  40. Parker R, Song H.; ''The enzymes and control of eukaryotic mRNA turnover.''; PubMed Europe PMC Scholia
  41. Jen KY, Cheung VG.; ''Identification of novel p53 target genes in ionizing radiation response.''; PubMed Europe PMC Scholia
  42. Gupta S, Radha V, Furukawa Y, Swarup G.; ''Direct transcriptional activation of human caspase-1 by tumor suppressor p53.''; PubMed Europe PMC Scholia
  43. Shao S, Wang Y, Jin S, Song Y, Wang X, Fan W, Zhao Z, Fu M, Tong T, Dong L, Fan F, Xu N, Zhan Q.; ''Gadd45a interacts with aurora-A and inhibits its kinase activity.''; PubMed Europe PMC Scholia
  44. Jain N, Gupta S, Sudhakar Ch, Radha V, Swarup G.; ''Role of p73 in regulating human caspase-1 gene transcription induced by interferon-{gamma} and cisplatin.''; PubMed Europe PMC Scholia
  45. Krause A, Hoffmann I.; ''Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication.''; PubMed Europe PMC Scholia
  46. Robles AI, Bemmels NA, Foraker AB, Harris CC.; ''APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis.''; PubMed Europe PMC Scholia
  47. Attardi LD, Reczek EE, Cosmas C, Demicco EG, McCurrach ME, Lowe SW, Jacks T.; ''PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family.''; PubMed Europe PMC Scholia
  48. Miyashita T, Reed JC.; ''Tumor suppressor p53 is a direct transcriptional activator of the human bax gene.''; PubMed Europe PMC Scholia
  49. Contente A, Dittmer A, Koch MC, Roth J, Dobbelstein M.; ''A polymorphic microsatellite that mediates induction of PIG3 by p53.''; PubMed Europe PMC Scholia
  50. O'Farrell PH.; ''Triggering the all-or-nothing switch into mitosis.''; PubMed Europe PMC Scholia
  51. Guo B, Godzik A, Reed JC.; ''Bcl-G, a novel pro-apoptotic member of the Bcl-2 family.''; PubMed Europe PMC Scholia
  52. Schilling T, Schleithoff ES, Kairat A, Melino G, Stremmel W, Oren M, Krammer PH, Müller M.; ''Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family.''; PubMed Europe PMC Scholia
  53. Connell-Crowley L, Harper JW, Goodrich DW.; ''Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation.''; PubMed Europe PMC Scholia
  54. Brough D, Rothwell NJ.; ''Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death.''; PubMed Europe PMC Scholia
  55. Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox LS.; ''Characterisation of the interaction between PCNA and Gadd45.''; PubMed Europe PMC Scholia
  56. Celardo I, Grespi F, Antonov A, Bernassola F, Garabadgiu AV, Melino G, Amelio I.; ''Caspase-1 is a novel target of p63 in tumor suppression.''; PubMed Europe PMC Scholia
  57. Wang X.; ''The expanding role of mitochondria in apoptosis.''; PubMed Europe PMC Scholia
  58. Espinosa JM, Verdun RE, Emerson BM.; ''p53 functions through stress- and promoter-specific recruitment of transcription initiation components before and after DNA damage.''; PubMed Europe PMC Scholia
  59. Wang G, Jiang Q, Zhang C.; ''The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle.''; PubMed Europe PMC Scholia
  60. Wu L, Timmers C, Maiti B, Saavedra HI, Sang L, Chong GT, Nuckolls F, Giangrande P, Wright FA, Field SJ, Greenberg ME, Orkin S, Nevins JR, Robinson ML, Leone G.; ''The E2F1-3 transcription factors are essential for cellular proliferation.''; PubMed Europe PMC Scholia
  61. Park WR, Nakamura Y.; ''p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway.''; PubMed Europe PMC Scholia
  62. Kim HL, Kim SU, Seo YR.; ''A novel role for Gadd45α in base excision repair: modulation of APE1 activity by the direct interaction of Gadd45α with PCNA.''; PubMed Europe PMC Scholia
  63. Wu M, Xu LG, Su T, Tian Y, Zhai Z, Shu HB.; ''AMID is a p53-inducible gene downregulated in tumors.''; PubMed Europe PMC Scholia
  64. Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y, Monden M, Nakamura Y.; ''p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis.''; PubMed Europe PMC Scholia
  65. Duriez C, Falette N, Audoynaud C, Moyret-Lalle C, Bensaad K, Courtois S, Wang Q, Soussi T, Puisieux A.; ''The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene.''; PubMed Europe PMC Scholia
  66. Lin Y, Ma W, Benchimol S.; ''Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis.''; PubMed Europe PMC Scholia
  67. Murray-Zmijewski F, Slee EA, Lu X.; ''A complex barcode underlies the heterogeneous response of p53 to stress.''; PubMed Europe PMC Scholia
  68. Samuels-Lev Y, O'Connor DJ, Bergamaschi D, Trigiante G, Hsieh JK, Zhong S, Campargue I, Naumovski L, Crook T, Lu X.; ''ASPP proteins specifically stimulate the apoptotic function of p53.''; PubMed Europe PMC Scholia
  69. Aksoy O, Chicas A, Zeng T, Zhao Z, McCurrach M, Wang X, Lowe SW.; ''The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescence.''; PubMed Europe PMC Scholia
  70. Li CQ, Robles AI, Hanigan CL, Hofseth LJ, Trudel LJ, Harris CC, Wogan GN.; ''Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53.''; PubMed Europe PMC Scholia
  71. Scoumanne A, Cho SJ, Zhang J, Chen X.; ''The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stability.''; PubMed Europe PMC Scholia
  72. Carvajal LA, Hamard PJ, Tonnessen C, Manfredi JJ.; ''E2F7, a novel target, is up-regulated by p53 and mediates DNA damage-dependent transcriptional repression.''; PubMed Europe PMC Scholia
  73. Rouault JP, Prévôt D, Berthet C, Birot AM, Billaud M, Magaud JP, Corbo L.; ''Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complex.''; PubMed Europe PMC Scholia
  74. Sadasivam S, Gupta S, Radha V, Batta K, Kundu TK, Swarup G.; ''Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis.''; PubMed Europe PMC Scholia
  75. Lees JA, Saito M, Vidal M, Valentine M, Look T, Harlow E, Dyson N, Helin K.; ''The retinoblastoma protein binds to a family of E2F transcription factors.''; PubMed Europe PMC Scholia
  76. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N.; ''Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.''; PubMed Europe PMC Scholia
  77. Chittenden T, Livingston DM, Kaelin WG.; ''The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein.''; PubMed Europe PMC Scholia
  78. Vidal A, Koff A.; ''Cell-cycle inhibitors: three families united by a common cause.''; PubMed Europe PMC Scholia
  79. Chang J, Cizmecioglu O, Hoffmann I, Rhee K.; ''PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle.''; PubMed Europe PMC Scholia
  80. Cobrinik D.; ''Pocket proteins and cell cycle control.''; PubMed Europe PMC Scholia
  81. Varrault A, Ciani E, Apiou F, Bilanges B, Bilanges B, Hoffmann A, Pantaloni C, Bockaert J, Spengler D, Journot L.; ''hZAC encodes a zinc finger protein with antiproliferative properties and maps to a chromosomal region frequently lost in cancer.''; PubMed Europe PMC Scholia
  82. Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A, Trouche D.; ''The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase.''; PubMed Europe PMC Scholia
  83. Houseley J, Tollervey D.; ''The many pathways of RNA degradation.''; PubMed Europe PMC Scholia
  84. Sánchez R, Pantoja-Uceda D, Prieto J, Diercks T, Marcaida MJ, Montoya G, Campos-Olivas R, Blanco FJ.; ''Solution structure of human growth arrest and DNA damage 45alpha (Gadd45alpha) and its interactions with proliferating cell nuclear antigen (PCNA) and Aurora A kinase.''; PubMed Europe PMC Scholia
  85. Guan KL, Jenkins CW, Li Y, O'Keefe CL, Noh S, Wu X, Zariwala M, Matera AG, Xiong Y.; ''Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4.''; PubMed Europe PMC Scholia
  86. Guan KL, Jenkins CW, Li Y, Nichols MA, Wu X, O'Keefe CL, Matera AG, Xiong Y.; ''Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function.''; PubMed Europe PMC Scholia
  87. Davies L, Gray D, Spiller D, White MR, Damato B, Grierson I, Paraoan L.; ''P53 apoptosis mediator PERP: localization, function and caspase activation in uveal melanoma.''; PubMed Europe PMC Scholia
  88. Di Stefano L, Jensen MR, Helin K.; ''E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes.''; PubMed Europe PMC Scholia
  89. Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT, Mills AA, Attardi LD.; ''Perp is a p63-regulated gene essential for epithelial integrity.''; PubMed Europe PMC Scholia
  90. Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS, Wang M, Liang P.; ''NDRG1 is necessary for p53-dependent apoptosis.''; PubMed Europe PMC Scholia
  91. Liu X, Yue P, Khuri FR, Sun SY.; ''p53 upregulates death receptor 4 expression through an intronic p53 binding site.''; PubMed Europe PMC Scholia
  92. Garneau NL, Wilusz J, Wilusz CJ.; ''The highways and byways of mRNA decay.''; PubMed Europe PMC Scholia
  93. Kruiswijk F, Labuschagne CF, Vousden KH.; ''p53 in survival, death and metabolic health: a lifeguard with a licence to kill.''; PubMed Europe PMC Scholia
  94. Chan TA, Hermeking H, Lengauer C, Kinzler KW, Vogelstein B.; ''14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage.''; PubMed Europe PMC Scholia
  95. Syed N, Smith P, Sullivan A, Spender LC, Dyer M, Karran L, O'Nions J, Allday M, Hoffmann I, Crawford D, Griffin B, Farrell PJ, Crook T.; ''Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies.''; PubMed Europe PMC Scholia
  96. Wilusz CJ, Wormington M, Peltz SW.; ''The cap-to-tail guide to mRNA turnover.''; PubMed Europe PMC Scholia
  97. Bahassi el M, Hennigan RF, Myer DL, Stambrook PJ.; ''Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation.''; PubMed Europe PMC Scholia
  98. Moore MJ.; ''From birth to death: the complex lives of eukaryotic mRNAs.''; PubMed Europe PMC Scholia
  99. Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR.; ''The E2F transcription factor is a cellular target for the RB protein.''; PubMed Europe PMC Scholia
  100. Patel S, George R, Autore F, Fraternali F, Ladbury JE, Nikolova PV.; ''Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax.''; PubMed Europe PMC Scholia
  101. Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S, Kinzler KW, Vogelstein B.; ''14-3-3sigma is a p53-regulated inhibitor of G2/M progression.''; PubMed Europe PMC Scholia
  102. Serrano M, Hannon GJ, Beach D.; ''A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.''; PubMed Europe PMC Scholia
  103. Bagchi S, Weinmann R, Raychaudhuri P.; ''The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F.''; PubMed Europe PMC Scholia
  104. Takimoto R, El-Deiry WS.; ''Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site.''; PubMed Europe PMC Scholia
  105. Ingermann AR, Yang YF, Han J, Mikami A, Garza AE, Mohanraj L, Fan L, Idowu M, Ware JL, Kim HS, Lee DY, Oh Y.; ''Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer.''; PubMed Europe PMC Scholia
  106. Pandit SK, Westendorp B, Nantasanti S, van Liere E, Tooten PC, Cornelissen PW, Toussaint MJ, Lamers WH, de Bruin A.; ''E2F8 is essential for polyploidization in mammalian cells.''; PubMed Europe PMC Scholia
  107. Zhu J, Chen X.; ''MCG10, a novel p53 target gene that encodes a KH domain RNA-binding protein, is capable of inducing apoptosis and cell cycle arrest in G(2)-M.''; PubMed Europe PMC Scholia
  108. Nakano K, Vousden KH.; ''PUMA, a novel proapoptotic gene, is induced by p53.''; PubMed Europe PMC Scholia
  109. Li J, Ran C, Li E, Gordon F, Comstock G, Siddiqui H, Cleghorn W, Chen HZ, Kornacker K, Liu CG, Pandit SK, Khanizadeh M, Weinstein M, Leone G, de Bruin A.; ''Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development.''; PubMed Europe PMC Scholia
  110. St Clair S, Giono L, Varmeh-Ziaie S, Resnick-Silverman L, Liu WJ, Padi A, Dastidar J, DaCosta A, Mattia M, Manfredi JJ.; ''DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25C promoter.''; PubMed Europe PMC Scholia
  111. Bruinsma W, Raaijmakers JA, Medema RH.; ''Switching Polo-like kinase-1 on and off in time and space.''; PubMed Europe PMC Scholia
  112. Maiti B, Li J, de Bruin A, Gordon F, Timmers C, Opavsky R, Patil K, Tuttle J, Cleghorn W, Leone G.; ''Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation.''; PubMed Europe PMC Scholia
  113. Horiuchi M, Takeuchi K, Noda N, Muroya N, Suzuki T, Nakamura T, Kawamura-Tsuzuku J, Takahasi K, Yamamoto T, Inagaki F.; ''Structural basis for the antiproliferative activity of the Tob-hCaf1 complex.''; PubMed Europe PMC Scholia
  114. Mantovani F, Zannini A, Rustighi A, Del Sal G.; ''Interaction of p53 with prolyl isomerases: Healthy and unhealthy relationships.''; PubMed Europe PMC Scholia
  115. Meek DW, Anderson CW.; ''Posttranslational modification of p53: cooperative integrators of function.''; PubMed Europe PMC Scholia
  116. Doidge R, Mittal S, Aslam A, Winkler GS.; ''The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex.''; PubMed Europe PMC Scholia
  117. An W, Kim J, Roeder RG.; ''Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53.''; PubMed Europe PMC Scholia
  118. Riley T, Sontag E, Chen P, Levine A.; ''Transcriptional control of human p53-regulated genes.''; PubMed Europe PMC Scholia
  119. Ihrie RA, Reczek E, Horner JS, Khachatrian L, Sage J, Jacks T, Attardi LD.; ''Perp is a mediator of p53-dependent apoptosis in diverse cell types.''; PubMed Europe PMC Scholia
  120. Cheng M, Sexl V, Sherr CJ, Roussel MF.; ''Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1).''; PubMed Europe PMC Scholia
  121. Sadasivam S, DeCaprio JA.; ''The DREAM complex: master coordinator of cell cycle-dependent gene expression.''; PubMed Europe PMC Scholia
  122. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ.; ''The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.''; PubMed Europe PMC Scholia
  123. Santiago A, Li D, Zhao LY, Godsey A, Liao D.; ''p53 SUMOylation promotes its nuclear export by facilitating its release from the nuclear export receptor CRM1.''; PubMed Europe PMC Scholia
  124. Rouault JP, Falette N, Guéhenneux F, Guillot C, Rimokh R, Wang Q, Berthet C, Moyret-Lalle C, Savatier P, Pain B, Shaw P, Berger R, Samarut J, Magaud JP, Ozturk M, Samarut C, Puisieux A.; ''Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway.''; PubMed Europe PMC Scholia
  125. Hannon GJ, Beach D.; ''p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest.''; PubMed Europe PMC Scholia
  126. Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn JC, Iovanna JL, Dusetti NJ.; ''TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity.''; PubMed Europe PMC Scholia
  127. MacLachlan TK, El-Deiry WS.; ''Apoptotic threshold is lowered by p53 transactivation of caspase-6.''; PubMed Europe PMC Scholia
  128. Bergamaschi D, Samuels Y, Jin B, Duraisingham S, Crook T, Lu X.; ''ASPP1 and ASPP2: common activators of p53 family members.''; PubMed Europe PMC Scholia
  129. Fei P, Wang W, Kim SH, Wang S, Burns TF, Sax JK, Buzzai M, Dicker DT, McKenna WG, Bernhard EJ, El-Deiry WS.; ''Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth.''; PubMed Europe PMC Scholia
  130. Giam M, Okamoto T, Mintern JD, Strasser A, Bouillet P.; ''Bcl-2 family member Bcl-G is not a proapoptotic protein.''; PubMed Europe PMC Scholia
  131. Saigusa K, Imoto I, Tanikawa C, Aoyagi M, Ohno K, Nakamura Y, Inazawa J.; ''RGC32, a novel p53-inducible gene, is located on centrosomes during mitosis and results in G2/M arrest.''; PubMed Europe PMC Scholia
  132. Kruse JP, Gu W.; ''Modes of p53 regulation.''; PubMed Europe PMC Scholia
  133. Parry D, Bates S, Mann DJ, Peters G.; ''Lack of cyclin D-Cdk complexes in Rb-negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product.''; PubMed Europe PMC Scholia
  134. Wilson AM, Morquette B, Abdouh M, Unsain N, Barker PA, Feinstein E, Bernier G, Di Polo A.; ''ASPP1/2 regulate p53-dependent death of retinal ganglion cells through PUMA and Fas/CD95 activation in vivo.''; PubMed Europe PMC Scholia
  135. Zhang AH, Rao JN, Zou T, Liu L, Marasa BS, Xiao L, Chen J, Turner DJ, Wang JY.; ''p53-dependent NDRG1 expression induces inhibition of intestinal epithelial cell proliferation but not apoptosis after polyamine depletion.''; PubMed Europe PMC Scholia
  136. Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ.; ''Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.''; PubMed Europe PMC Scholia
  137. Wang L, Xing H, Tian Z, Peng L, Li Y, Tang K, Rao Q, Wang M, Wang J.; ''iASPPsv antagonizes apoptosis induced by chemotherapeutic agents in MCF-7 cells and mouse thymocytes.''; PubMed Europe PMC Scholia
  138. Taira N, Nihira K, Yamaguchi T, Miki Y, Yoshida K.; ''DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage.''; PubMed Europe PMC Scholia
  139. Dupressoir A, Morel AP, Barbot W, Loireau MP, Corbo L, Heidmann T.; ''Identification of four families of yCCR4- and Mg2+-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding.''; PubMed Europe PMC Scholia


View all...
114728view16:21, 25 January 2021ReactomeTeamReactome version 75
113172view11:23, 2 November 2020ReactomeTeamReactome version 74
112400view15:33, 9 October 2020ReactomeTeamReactome version 73
101304view11:19, 1 November 2018ReactomeTeamreactome version 66
100841view20:50, 31 October 2018ReactomeTeamreactome version 65
100382view19:25, 31 October 2018ReactomeTeamreactome version 64
99929view16:08, 31 October 2018ReactomeTeamreactome version 63
99484view14:41, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99137view12:40, 31 October 2018ReactomeTeamreactome version 62
93809view13:37, 16 August 2017ReactomeTeamreactome version 61
93351view11:21, 9 August 2017ReactomeTeamreactome version 61
88397view15:19, 4 August 2016FehrhartOntology Term : 'regulatory pathway' added !
88396view15:19, 4 August 2016FehrhartOntology Term : 'cell cycle pathway' added !
86435view09:18, 11 July 2016ReactomeTeamNew pathway

External references


View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ARID3A Gene ProteinENSG00000116017 (Ensembl)
ARID3A GeneGeneProductENSG00000116017 (Ensembl)
ARID3AProteinQ99856 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
AURKA ProteinO14965 (Uniprot-TrEMBL)
AURKAProteinO14965 (Uniprot-TrEMBL)
BAX ProteinQ07812 (Uniprot-TrEMBL)