Regulation of TP53 Activity through Phosphorylation (Homo sapiens)

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1, 4, 8, 11, 14...41, 4870355, 8024, 88, 9366, 698, 117021, 7515574, 81, 95, 98805725, 43, 44, 59, 6120, 92811425, 32, 43, 538036, 6266, 694539, 631, 6, 17, 85, 10216cytosolnucleoplasmTAF7L p-S15,S392-TP53Tetramerp-T714,T734-BARD1 Oxidative StressInduced SenescenceCSNK2A1 p-S317,S345-CHEK1UBC(229-304) p-S1981,Ac-K3016-ATMTAF6 TAF10 CSNK2A2 STK11p-S988,S1387,S1423,S1524,S1547-BRCA1 RFC4 CCNA2 p-S166,S188-MDM2dimer,p-S166,S188-MDM2:MDM4CSNK2B RAD9A PRKAG2 p-T55-TP53 ADPp-S15,S392-TP53 p-T180,Y182-MAPK11 MDM4 TP53Tetramer:STK11:NUAK1TAF4 PRKAG3 Activated AMPKheterotrimerUBB(153-228) TAF11 TAF9B CSNK2A2 ADPADPATPp-T288-AURKA:TPX2RPA1 HIPK1ADPPRKAB2 UbNUAK1 p-S15-TP53 RPS27A(1-76) TAF4B DNA2 Casein kinase IIAURKB:NOC2L:p-S15,S20,S269,T284-TP53PRKAB1 p-S15,S20-TP53 ATPPIN1 MRE11A STK11 TP53INP1SUPT16H p-S15,S20,S46-TP53Tetramerp-T180,Y182-MAPK14 AURKBTOP3A AURKB:NOC2L:p-S15,S20-TP53WRN PRKAG1 CSNK2A1 p-S15,S20-TP53 ATPp-T211-NUAK1 RFC5 TP53 CSNK2B p-S37-TP53 ATPp-T183-PRKAA1 ADPPLK3p-S343-NBN UBC(457-532) FACT complexp-S315-TP53 CCNA1 TFIIDEXO1 TP53INP1 TP53Tetramer:STK11:p-T211-NUAK1UBC(533-608) p-S15,S20-TP53 p-S15,S20,S269,T284-TP53 TAF9 ATR p-S15,S20,S46-TP53 AURKB TAF3 UBC(153-228) AURKB TAF5 NUAK1ADPRAD9B TP53 Tetramer:HIPK1RAD50 CCNA:p-T160-CDK2ATPTOPBP1 SSRP1 UBB(1-76) TAF12 ATR:ATRIP:RPA:3'overhangingssDNA-DSBs:p-MRN:p-S1981,Ac-K3016-ATM:KAT5:BRCA1-C complex:EXO1,DNA2:BLM,WRN:p-S990,Ac-K1249-BRIP1:RAD17:RFC:RAD9:HUS1:RAD1:RHNO1:TOPBP1p-S315-TP53 TetramerATPRAD17 p-HIPK2 p-T160-CDK2 p-S15-TP53 Tetramerp-T172-PRKAA2 p-T106,S442-DYRK23' overhanging DNA at resected DSB ends NOC2L UBC(1-76) UBA52(1-76) TBP TP53 p-HIPK2:PIN1NOC2L ADPp-T288-AURKA p-S166,S188-MDM2 RFC3 p-S15,S20-TP53TetramerAMP RAD1 RHNO1 ADPCK2:FACTTP53INP1:p-HIPK2:PIN1:p-S15,S20-TP53ADPATPp-S15,S20,S392-TP53 NOC2Lphospho-p38MAPK:p-T-182-MAPKAPK5ATRIP TPX2 TAF1L p-Y15,S159-CDK5 RFC2 p-S15,S20,S392-TP53TetramerATPRPA2 DYRK2RMI1 p-S1981,Ac-K3016-ATM UBB(77-152) p-S327,T847,T859-RBBP8 TAF1 UBC(77-152) RPA3 BLM p-T211-NUAK1TP53 ATPADPp-T182-MAPKAPK5 p-T55-TP53 Tetramerp-S,3T-CHEK2p-S990,Ac-K1249-BRIP1 p-S37-TP53 Tetramerp-S15,S20-TP53 p-HIPK2 TP53RKRMI2 ATPp-S15,S33,S46-TP53TetramerSUPT16H ADPADPNOC2L:p-S15,S20-TP53NOC2L p-Y15,S159-CDK5:CDK5R1 (99-307)TAF7 UBC(381-456) PolyUb-DYRK2CDK5R1(99-307) TP53 p-S15,S33,S46-TP53 UBC(305-380) ATPKAT5 HUS1 PIN1 TAF13 STK11 TAF2 HIPK1 ATPTP53 TetramerSSRP1 UBC(609-684) Regulation of TP53Expression andDegradation142, 9, 10, 13, 23...705, 8041, 48802, 37, 56193, 7, 12, 13, 16...170436044, 5976, 77, 91, 946245


Description

Phosphorylation of TP53 (p53) at the N-terminal serine residues S15 and S20 plays a critical role in protein stabilization as phosphorylation at these sites interferes with binding of the ubiquitin ligase MDM2 to TP53. Several different kinases can phosphorylate TP53 at S15 and S20. In response to double strand DNA breaks, S15 is phosphorylated by ATM (Banin et al. 1998, Canman et al. 1998, Khanna et al. 1998), and S20 by CHEK2 (Chehab et al. 1999, Chehab et al. 2000, Hirao et al. 2000). DNA damage or other types of genotoxic stress, such as stalled replication forks, can trigger ATR-mediated phosphorylation of TP53 at S15 (Lakin et al. 1999, Tibbetts et al. 1999) and CHEK1-mediated phosphorylation of TP53 at S20 (Shieh et al. 2000). In response to various types of cell stress, NUAK1 (Hou et al. 2011), CDK5 (Zhang et al. 2002, Lee et al. 2007, Lee et al. 2008), AMPK (Jones et al. 2005) and TP53RK (Abe et al. 2001, Facchin et al. 2003) can phosphorylate TP53 at S15, while PLK3 (Xie, Wang et al. 2001, Xie, Wu et al. 2001) can phosphorylate TP53 at S20.

Phosphorylation of TP53 at serine residue S46 promotes transcription of TP53-regulated apoptotic genes rather than cell cycle arrest genes. Several kinases can phosphorylate S46 of TP53, including ATM-activated DYRK2, which, like TP53, is targeted for degradation by MDM2 (Taira et al. 2007, Taira et al. 2010). TP53 is also phosphorylated at S46 by HIPK2 in the presence of the TP53 transcriptional target TP53INP1 (D'Orazi et al. 2002, Hofmann et al. 2002, Tomasini et al. 2003). CDK5, in addition to phosphorylating TP53 at S15, also phosphorylates it at S33 and S46, which promotes neuronal cell death (Lee et al. 2007).<p>MAPKAPK5 (PRAK) phosphorylates TP53 at serine residue S37, promoting cell cycle arrest and cellular senescence in response to oncogenic RAS signaling (Sun et al. 2007).<p>NUAK1 phosphorylates TP53 at S15 and S392, and phosphorylation at S392 may contribute to TP53-mediated transcriptional activation of cell cycle arrest genes (Hou et al. 2011). S392 of TP53 is also phosphorylated by the complex of casein kinase II (CK2) bound to the FACT complex, enhancing transcriptional activity of TP53 in response to UV irradiation (Keller et al. 2001, Keller and Lu 2002).<p>The activity of TP53 is inhibited by phosphorylation at serine residue S315, which enhances MDM2 binding and degradation of TP53. S315 of TP53 is phosphorylated by Aurora kinase A (AURKA) (Katayama et al. 2004) and CDK2 (Luciani et al. 2000). Interaction with MDM2 and the consequent TP53 degradation is also increased by phosphorylation of TP53 threonine residue T55 by the transcription initiation factor complex TFIID (Li et al. 2004).<p>Aurora kinase B (AURKB) has been shown to phosphorylate TP53 at serine residue S269 and threonine residue T284, which is possibly facilitated by the binding of the NIR co-repressor. AURKB-mediated phosphorylation was reported to inhibit TP53 transcriptional activity through an unknown mechanism (Wu et al. 2011). A putative direct interaction between TP53 and AURKB has also been described and linked to TP53 phosphorylation and S183, T211 and S215 and TP53 degradation (Gully et al. 2012). View original pathway at:Reactome.</div>

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Pathway is converted from Reactome ID: 6804756
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Reactome version: 61
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Reactome Author: Orlic-Milacic, Marija

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Bibliography

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  93. Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, Dröge W, Will H, Schmitz ML.; ''Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2.''; PubMed
  94. Raingeaud J, Whitmarsh AJ, Barrett T, Dérijard B, Davis RJ.; ''MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway.''; PubMed
  95. New L, Jiang Y, Han J.; ''Regulation of PRAK subcellular location by p38 MAP kinases.''; PubMed
  96. Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y.; ''pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene.''; PubMed
  97. Voncken JW, Niessen H, Neufeld B, Rennefahrt U, Dahlmans V, Kubben N, Holzer B, Ludwig S, Rapp UR.; ''MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1.''; PubMed
  98. Cheng Q, Cross B, Li B, Chen L, Li Z, Chen J.; ''Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage.''; PubMed
  99. Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S.; ''Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53.''; PubMed
  100. Lukas SM, Kroe RR, Wildeson J, Peet GW, Frego L, Davidson W, Ingraham RH, Pargellis CA, Labadia ME, Werneburg BG.; ''Catalysis and function of the p38 alpha.MK2a signaling complex.''; PubMed
  101. Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, Gu W.; ''Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization.''; PubMed
  102. Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD.; ''Activation of the ATM kinase by ionizing radiation and phosphorylation of p53.''; PubMed
  103. Sharma P, Sharma M, Amin ND, Albers RW, Pant HC.; ''Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation.''; PubMed
  104. Mizukami Y, Yoshioka K, Morimoto S, Yoshida K.; ''A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion.''; PubMed
  105. Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K.; ''EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.''; PubMed

History

View all...
CompareRevisionActionTimeUserComment
101393view11:28, 1 November 2018ReactomeTeamreactome version 66
100931view21:04, 31 October 2018ReactomeTeamreactome version 65
100469view19:38, 31 October 2018ReactomeTeamreactome version 64
100015view16:21, 31 October 2018ReactomeTeamreactome version 63
99568view14:54, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94038view13:53, 16 August 2017ReactomeTeamreactome version 61
93661view11:30, 9 August 2017ReactomeTeamreactome version 61
88149view13:02, 26 July 2016RyanmillerOntology Term : 'transcription pathway' added !
88148view13:02, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86780view09:26, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
3' overhanging DNA at resected DSB ends R-NUL-75156 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
AMP MetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
ATR ProteinQ13535 (Uniprot-TrEMBL)
ATR:ATRIP:RPA:3'

overhanging

ssDNA-DSBs:p-MRN:p-S1981,Ac-K3016-ATM:KAT5:BRCA1-C complex:EXO1,DNA2:BLM,WRN:p-S990,Ac-K1249-BRIP1:RAD17:RFC:RAD9:HUS1:RAD1:RHNO1:TOPBP1
ComplexR-HSA-5685039 (Reactome)
ATRIP ProteinQ8WXE1 (Uniprot-TrEMBL)
AURKB ProteinQ96GD4 (Uniprot-TrEMBL)
AURKB:NOC2L:p-S15,S20,S269,T284-TP53ComplexR-HSA-6805128 (Reactome)
AURKB:NOC2L:p-S15,S20-TP53ComplexR-HSA-6805123 (Reactome)
AURKBProteinQ96GD4 (Uniprot-TrEMBL)
Activated AMPK heterotrimerComplexR-HSA-6805467 (Reactome)
BLM ProteinP54132 (Uniprot-TrEMBL)
CCNA1 ProteinP78396 (Uniprot-TrEMBL)
CCNA2 ProteinP20248 (Uniprot-TrEMBL)
CCNA:p-T160-CDK2ComplexR-HSA-187952 (Reactome)
CDK5R1(99-307) ProteinQ15078 (Uniprot-TrEMBL)
CK2:FACTComplexR-HSA-6805062 (Reactome)
CSNK2A1 ProteinP68400 (Uniprot-TrEMBL)
CSNK2A2 ProteinP19784 (Uniprot-TrEMBL)
CSNK2B ProteinP67870 (Uniprot-TrEMBL)
Casein kinase IIComplexR-HSA-6805066 (Reactome)
DNA2 ProteinP51530 (Uniprot-TrEMBL)
DYRK2ProteinQ92630 (Uniprot-TrEMBL)
EXO1 ProteinQ9UQ84 (Uniprot-TrEMBL)
FACT complexComplexR-HSA-112417 (Reactome)
HIPK1 ProteinQ86Z02 (Uniprot-TrEMBL)
HIPK1ProteinQ86Z02 (Uniprot-TrEMBL)
HUS1 ProteinO60921 (Uniprot-TrEMBL)
KAT5 ProteinQ92993 (Uniprot-TrEMBL)
MDM4 ProteinO15151 (Uniprot-TrEMBL)
MRE11A ProteinP49959 (Uniprot-TrEMBL)
NOC2L ProteinQ9Y3T9 (Uniprot-TrEMBL)
NOC2L:p-S15,S20-TP53ComplexR-HSA-3222134 (Reactome)
NOC2LProteinQ9Y3T9 (Uniprot-TrEMBL)
NUAK1 ProteinO60285 (Uniprot-TrEMBL)
NUAK1ProteinO60285 (Uniprot-TrEMBL)
Oxidative Stress Induced SenescencePathwayR-HSA-2559580 (Reactome) Oxidative stress, caused by increased concentration of reactive oxygen species (ROS) in the cell, can happen as a consequence of mitochondrial dysfunction induced by the oncogenic RAS (Moiseeva et al. 2009) or independent of oncogenic signaling. Prolonged exposure to interferon-beta (IFNB, IFN-beta) also results in ROS increase (Moiseeva et al. 2006). ROS oxidize thioredoxin (TXN), which causes TXN to dissociate from the N-terminus of MAP3K5 (ASK1), enabling MAP3K5 to become catalytically active (Saitoh et al. 1998). ROS also stimulate expression of Ste20 family kinases MINK1 (MINK) and TNIK through an unknown mechanism, and MINK1 and TNIK positively regulate MAP3K5 activation (Nicke et al. 2005).


MAP3K5 phosphorylates and activates MAP2K3 (MKK3) and MAP2K6 (MKK6) (Ichijo et al. 1997, Takekawa et al. 2005), which act as p38 MAPK kinases, as well as MAP2K4 (SEK1) (Ichijo et al. 1997, Matsuura et al. 2002), which, together with MAP2K7 (MKK7), acts as a JNK kinase.


MKK3 and MKK6 phosphorylate and activate p38 MAPK alpha (MAPK14) and beta (MAPK11) (Raingeaud et al. 1996), enabling p38 MAPKs to phosphorylate and activate MAPKAPK2 (MK2) and MAPKAPK3 (MK3) (Ben-Levy et al. 1995, Clifton et al. 1996, McLaughlin et al. 1996, Sithanandam et al. 1996, Meng et al. 2002, Lukas et al. 2004, White et al. 2007), as well as MAPKAPK5 (PRAK) (New et al. 1998 and 2003, Sun et al. 2007).


Phosphorylation of JNKs (MAPK8, MAPK9 and MAPK10) by MAP3K5-activated MAP2K4 (Deacon and Blank 1997, Fleming et al. 2000) allows JNKs to migrate to the nucleus (Mizukami et al. 1997) where they phosphorylate JUN. Phosphorylated JUN binds FOS phosphorylated by ERK1 or ERK2, downstream of activated RAS (Okazaki and Sagata 1995, Murphy et al. 2002), forming the activated protein 1 (AP-1) complex (FOS:JUN heterodimer) (Glover and Harrison 1995, Ainbinder et al. 1997).


Activation of p38 MAPKs and JNKs downstream of MAP3K5 (ASK1) ultimately converges on transcriptional regulation of CDKN2A locus. In dividing cells, nucleosomes bound to the CDKN2A locus are trimethylated on lysine residue 28 of histone H3 (HIST1H3A) by the Polycomb repressor complex 2 (PRC2), creating the H3K27Me3 (Me3K-28-HIST1H3A) mark (Bracken et al. 2007, Kotake et al. 2007). The expression of Polycomb constituents of PRC2 (Kuzmichev et al. 2002) - EZH2, EED and SUZ12 - and thereby formation of the PRC2, is positively regulated in growing cells by E2F1, E2F2 and E2F3 (Weinmann et al. 2001, Bracken et al. 2003). H3K27Me3 mark serves as a docking site for the Polycomb repressor complex 1 (PRC1) that contains BMI1 (PCGF4) and is therefore named PRC1.4, leading to the repression of transcription of p16-INK4A and p14-ARF from the CDKN2A locus, where PCR1.4 mediated repression of p14-ARF transcription in humans may be context dependent (Voncken et al. 2005, Dietrich et al. 2007, Agherbi et al. 2009, Gao et al. 2012). MAPKAPK2 and MAPKAPK3, activated downstream of the MAP3K5-p38 MAPK cascade, phosphorylate BMI1 of the PRC1.4 complex, leading to dissociation of PRC1.4 complex from the CDKN2A locus and upregulation of p14-ARF transcription (Voncken et al. 2005). AP-1 transcription factor, formed as a result of MAP3K5-JNK signaling, as well as RAS signaling, binds the promoter of KDM6B (JMJD3) gene and stimulates KDM6B expression. KDM6B is a histone demethylase that removes H3K27Me3 mark i.e. demethylates lysine K28 of HIST1H3A, thereby preventing PRC1.4 binding to the CDKN2A locus and allowing transcription of p16-INK4A (Agger et al. 2009, Barradas et al. 2009, Lin et al. 2012).


p16-INK4A inhibits phosphorylation-mediated inactivation of RB family members by CDK4 and CDK6, leading to cell cycle arrest (Serrano et al. 1993). p14-ARF inhibits MDM2-mediated degradation of TP53 (p53) (Zhang et al. 1998), which also contributes to cell cycle arrest in cells undergoing oxidative stress. In addition, phosphorylation of TP53 by MAPKAPK5 (PRAK) activated downstream of MAP3K5-p38 MAPK signaling, activates TP53 and contributes to cellular senescence (Sun et al. 2007).

PIN1 ProteinQ13526 (Uniprot-TrEMBL)
PLK3ProteinQ9H4B4 (Uniprot-TrEMBL)
PRKAB1 ProteinQ9Y478 (Uniprot-TrEMBL)
PRKAB2 ProteinO43741 (Uniprot-TrEMBL)
PRKAG1 ProteinP54619 (Uniprot-TrEMBL)
PRKAG2 ProteinQ9UGJ0 (Uniprot-TrEMBL)
PRKAG3 ProteinQ9UGI9 (Uniprot-TrEMBL)
PolyUb-DYRK2ProteinQ92630 (Uniprot-TrEMBL)
RAD1 ProteinO60671 (Uniprot-TrEMBL)
RAD17 ProteinO75943 (Uniprot-TrEMBL)
RAD50 ProteinQ92878 (Uniprot-TrEMBL)
RAD9A ProteinQ99638 (Uniprot-TrEMBL)
RAD9B ProteinQ6WBX8 (Uniprot-TrEMBL)
RFC2 ProteinP35250 (Uniprot-TrEMBL)
RFC3 ProteinP40938 (Uniprot-TrEMBL)
RFC4 ProteinP35249 (Uniprot-TrEMBL)
RFC5 ProteinP40937 (Uniprot-TrEMBL)
RHNO1 ProteinQ9BSD3 (Uniprot-TrEMBL)
RMI1 ProteinQ9H9A7 (Uniprot-TrEMBL)
RMI2 ProteinQ96E14 (Uniprot-TrEMBL)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
Regulation of TP53

Expression and

Degradation
PathwayR-HSA-6806003 (Reactome) TP53 (p53) tumor suppressor protein is a transcription factor that functions as a homotetramer (Jeffrey et al. 1995). The protein levels of TP53 are low in unstressed cells due to MDM2-mediated ubiquitination that triggers proteasome-mediated degradation of TP53 (Wu et al. 1993). The E3 ubiquitin ligase MDM2 functions as a homodimer/homo-oligomer or a heterodimer/hetero-oligomer with MDM4 (MDMX) (Linares et al. 2003, Toledo and Wahl 2007, Cheng et al. 2011, Wade et al. 2013).

Activating phosphorylation of TP53 at serine residues S15 and S20 in response to genotoxic stress disrupts TP53 interaction with MDM2. In contrast to MDM2, E3 ubiquitin ligases RNF34 (CARP1) and RFFL (CARP2) can ubiquitinate phosphorylated TP53 (Yang et al. 2007). Binding of MDM2 to TP53 is also inhibited by the tumor suppressor p14-ARF, transcribed from the CDKN2A gene in response to oncogenic signaling or oxidative stress (Zhang et al. 1998, Parisi et al. 2002, Voncken et al. 2005). Ubiquitin-dependant degradation of TP53 can also be promoted by PIRH2 (Leng et al. 2003) and COP1 (Dornan et al. 2004) ubiquitin ligases. HAUSP (USP7) can deubiquitinate TP53, contributing to TP53 stabilization (Li et al. 2002).

While post-translational regulation plays a prominent role, TP53 activity is also controlled at the level of promoter function (reviewed in Saldana-Meyer and Recillas-Targa 2011), mRNA stability and translation efficiency (Mahmoudi et al. 2009, Le et al. 2009, Takagi et al. 2005).

SSRP1 ProteinQ08945 (Uniprot-TrEMBL)
STK11 ProteinQ15831 (Uniprot-TrEMBL)
STK11ProteinQ15831 (Uniprot-TrEMBL)
SUPT16H ProteinQ9Y5B9 (Uniprot-TrEMBL) DSIF is a heterodimer consisting of hSPT4 (human homolog of yeast Spt4- p14) and hSPT5 (human homolog of yeast Spt5-p160). DSIF association with Pol II may be enabled by Spt5 binding to Pol II creating a scaffold for NELF binding (Wada et al.,1998). Spt5 subunit of DSIF can be phosphorylated by P-TEFb.
TAF1 ProteinP21675 (Uniprot-TrEMBL)
TAF10 ProteinQ12962 (Uniprot-TrEMBL)
TAF11 ProteinQ15544 (Uniprot-TrEMBL)
TAF12 ProteinQ16514 (Uniprot-TrEMBL)
TAF13 ProteinQ15543 (Uniprot-TrEMBL)
TAF1L ProteinQ8IZX4 (Uniprot-TrEMBL)
TAF2 ProteinQ6P1X5 (Uniprot-TrEMBL)
TAF3 ProteinQ5VWG9 (Uniprot-TrEMBL)
TAF4 ProteinO00268 (Uniprot-TrEMBL)
TAF4B ProteinQ92750 (Uniprot-TrEMBL)
TAF5 ProteinQ15542 (Uniprot-TrEMBL)
TAF6 ProteinP49848 (Uniprot-TrEMBL)
TAF7 ProteinQ15545 (Uniprot-TrEMBL)
TAF7L ProteinQ5H9L4 (Uniprot-TrEMBL)
TAF9 ProteinQ16594 (Uniprot-TrEMBL)
TAF9B ProteinQ9HBM6 (Uniprot-TrEMBL)
TBP ProteinP20226 (Uniprot-TrEMBL)
TFIIDComplexR-HSA-109626 (Reactome)
TOP3A ProteinQ13472 (Uniprot-TrEMBL)
TOPBP1 ProteinQ92547 (Uniprot-TrEMBL)
TP53 Tetramer:STK11:NUAK1ComplexR-HSA-6805036 (Reactome)
TP53 Tetramer:STK11:p-T211-NUAK1ComplexR-HSA-6805037 (Reactome)
TP53 ProteinP04637 (Uniprot-TrEMBL)
TP53 Tetramer:HIPK1ComplexR-HSA-6799433 (Reactome)
TP53 TetramerComplexR-HSA-3209194 (Reactome)
TP53INP1 ProteinQ96A56 (Uniprot-TrEMBL)
TP53INP1:p-HIPK2:PIN1:p-S15,S20-TP53ComplexR-HSA-3215242 (Reactome)
TP53INP1ProteinQ96A56 (Uniprot-TrEMBL)
TP53RKProteinQ96S44 (Uniprot-TrEMBL)
TPX2 ProteinQ9ULW0 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UbComplexR-HSA-68524 (Reactome)
WRN ProteinQ14191 (Uniprot-TrEMBL)
p-HIPK2 ProteinQ9H2X6 (Uniprot-TrEMBL)
p-HIPK2:PIN1ComplexR-HSA-6799392 (Reactome)
p-S,3T-CHEK2ProteinO96017 (Uniprot-TrEMBL)
p-S15,S20,S269,T284-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15,S20,S392-TP53 TetramerComplexR-HSA-6805046 (Reactome)
p-S15,S20,S392-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15,S20,S46-TP53 TetramerComplexR-HSA-6798371 (Reactome)
p-S15,S20,S46-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15,S20-TP53 TetramerComplexR-HSA-3222171 (Reactome)
p-S15,S20-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15,S33,S46-TP53 TetramerComplexR-HSA-6805275 (Reactome)
p-S15,S33,S46-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15,S392-TP53 TetramerComplexR-HSA-3222017 (Reactome)
p-S15,S392-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15-TP53 TetramerComplexR-HSA-349474 (Reactome)
p-S166,S188-MDM2

dimer,

p-S166,S188-MDM2:MDM4
ComplexR-HSA-6804745 (Reactome)
p-S166,S188-MDM2 ProteinQ00987 (Uniprot-TrEMBL)
p-S1981,Ac-K3016-ATM ProteinQ13315 (Uniprot-TrEMBL)
p-S1981,Ac-K3016-ATMProteinQ13315 (Uniprot-TrEMBL)
p-S315-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S315-TP53 TetramerComplexR-HSA-6805104 (Reactome)
p-S317,S345-CHEK1ProteinO14757 (Uniprot-TrEMBL)
p-S327,T847,T859-RBBP8 ProteinQ99708 (Uniprot-TrEMBL)
p-S343-NBN ProteinO60934 (Uniprot-TrEMBL)
p-S37-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S37-TP53 TetramerComplexR-HSA-3239015 (Reactome)
p-S988,S1387,S1423,S1524,S1547-BRCA1 ProteinP38398 (Uniprot-TrEMBL)
p-S990,Ac-K1249-BRIP1 ProteinQ9BX63 (Uniprot-TrEMBL)
p-T106,S442-DYRK2ProteinQ92630 (Uniprot-TrEMBL)
p-T160-CDK2 ProteinP24941 (Uniprot-TrEMBL)
p-T172-PRKAA2 ProteinP54646 (Uniprot-TrEMBL)
p-T180,Y182-MAPK11 ProteinQ15759 (Uniprot-TrEMBL)
p-T180,Y182-MAPK14 ProteinQ16539 (Uniprot-TrEMBL)