HDAC6 interactions (Homo sapiens)

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MeCP2 mutationPROS overproductionROSAlpha tubulinStathminPKC zeta5, 6, 1017, 18NADPHNOX2(NADPH Oxidase)NADP16, 22SOCS5miR-124STAT3219negative regulator of splicingAcetyl-CholesterolHDAC3mRNA ProcessingHDAC6FOXO3NR4A11, 815TAL1FOXO3BDNF8TDP-437, 11-14MECP2APOE4MECP24, 20HDAC6HDAC6Acetyl-2Alpha tubulinMECP2HDAC63, 19PNADHNAD


HDAC6 interactions - under construction

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  1. Ratti F, Ramond F, Moncollin V, Simonet T, Méjat A, Thomas JL, Streichenberger N, Gilquin B, Matthias P, Khochbin S, Sandri M, Schaeffer L; ''Histone deacetylase 6 is a FoxO transcription factor-dependent effector in skeletal muscle atrophy.''; J Biol Chem, 2015 PubMed
  2. Du Y, Seibenhener ML, Yan J, Jiang J, Wooten MC; ''aPKC phosphorylation of HDAC6 results in increased deacetylation activity.''; PLoS One, 2015 PubMed
  3. Cheng F, Lienlaf M, Wang HW, Perez-Villarroel P, Lee C, Woan K, Rock-Klotz J, Sahakian E, Woods D, Pinilla-Ibarz J, Kalin J, Tao J, Hancock W, Kozikowski A, Seto E, Villagra A, Sotomayor EM; ''A novel role for histone deacetylase 6 in the regulation of the tolerogenic STAT3/IL-10 pathway in APCs.''; J Immunol, 2014 PubMed
  4. Zahorakova D, Jachymova M, Kemlink D, Baxova A, Martasek P; ''APOE epsilon4: a potential modulation factor in Rett syndrome.''; J Child Neurol, 2010 PubMed
  5. Verma NK, Dourlat J, Davies AM, Long A, Liu WQ, Garbay C, Kelleher D, Volkov Y; ''STAT3-stathmin interactions control microtubule dynamics in migrating T-cells.''; J Biol Chem, 2009 PubMed
  6. Yan B, Xie S, Liu Z, Luo Y, Zhou J, Li D, Liu M; ''STAT3 association with microtubules and its activation are independent of HDAC6 activity.''; DNA Cell Biol, 2015 PubMed
  7. Sephton CF, Cenik C, Kucukural A, Dammer EB, Cenik B, Han Y, Dewey CM, Roth FP, Herz J, Peng J, Moore MJ, Yu G; ''Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes.''; J Biol Chem, 2011 PubMed
  8. Nott A, Cheng J, Gao F, Lin YT, Gjoneska E, Ko T, Minhas P, Zamudio AV, Meng J, Zhang F, Jin P, Tsai LH; ''Histone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavior.''; Nat Neurosci, 2016 PubMed
  9. Sephton CF, Cenik C, Kucukural A, Dammer EB, Cenik B, Han Y, Dewey CM, Roth FP, Herz J, Peng J, Moore MJ, Yu G; ''Identification of neuronal RNA targets of TDP-43-containing ribonucleoprotein complexes.''; J Biol Chem, 2011 PubMed
  10. Ng DC, Lin BH, Lim CP, Huang G, Zhang T, Poli V, Cao X; ''Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin.''; J Cell Biol, 2006 PubMed
  11. Odagiri S, Tanji K, Mori F, Miki Y, Kakita A, Takahashi H, Wakabayashi K; ''Brain expression level and activity of HDAC6 protein in neurodegenerative dementia.''; Biochem Biophys Res Commun, 2013 PubMed
  12. Fiesel FC, Schurr C, Weber SS, Kahle PJ; ''TDP-43 knockdown impairs neurite outgrowth dependent on its target histone deacetylase 6.''; Mol Neurodegener, 2011 PubMed
  13. Odagiri S, Tanji K, Mori F, Miki Y, Kakita A, Takahashi H, Wakabayashi K; ''Brain expression level and activity of HDAC6 protein in neurodegenerative dementia.''; Biochem Biophys Res Commun, 2013 PubMed
  14. Fiesel FC, Voigt A, Weber SS, Van den Haute C, Waldenmaier A, Görner K, Walter M, Anderson ML, Kern JV, Rasse TM, Schmidt T, Springer W, Kirchner R, Bonin M, Neumann M, Baekelandt V, Alunni-Fabbroni M, Schulz JB, Kahle PJ; ''Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6.''; EMBO J, 2010 PubMed
  15. Rambaud J, Desroches J, Balsalobre A, Drouin J; ''TIF1beta/KAP-1 is a coactivator of the orphan nuclear receptor NGFI-B/Nur77.''; J Biol Chem, 2009 PubMed
  16. Youn GS, Cho H, Kim D, Choi SY, Park J; ''Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes.''; Redox Biol, 2017 PubMed
  17. Kwan J, Wang H, Munk S, Xia L, Goldberg HJ, Whiteside CI; ''In high glucose protein kinase C-zeta activation is required for mesangial cell generation of reactive oxygen species.''; Kidney Int, 2005 PubMed
  18. Reinehr R, Görg B, Becker S, Qvartskhava N, Bidmon HJ, Selbach O, Haas HL, Schliess F, Häussinger D; ''Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices.''; Glia, 2007 PubMed
  19. M L, P PV, T K, M P, E S, J P, K V W, C L, F C, S D, M SKS, M M, A K, J PI, A S, J W, E M S, A V; ''Essential role of HDAC6 in the regulation of PD-L1 in melanoma.''; Mol Oncol, 2016 PubMed
  20. Sen A, Nelson TJ, Alkon DL; ''ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation.''; J Neurosci, 2015 PubMed
  21. Jiang S, Li C, McRae G, Lykken E, Sevilla J, Liu SQ, Wan Y, Li QJ; ''MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5.''; Sci Signal, 2014 PubMed
  22. Youn GS, Lee KW, Choi SY, Park J; ''Overexpression of HDAC6 induces pro-inflammatory responses by regulating ROS-MAPK-NF-κB/AP-1 signaling pathways in macrophages.''; Free Radic Biol Med, 2016 PubMed


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96736view15:03, 1 April 2018EgonwConverted interactions to regular arrows, which were not mim:conversions.
96719view16:24, 30 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
96670view15:23, 25 March 2018EgonwReset several arrows to Arrow, as they are not mim-conversions.
95969view13:33, 10 February 2018EgonwChanged a gene-gene mim-conversion to a regular arrow.
95968view13:27, 10 February 2018EgonwLarger box to make the text readable.
95072view14:19, 11 November 2017EgonwFixed character encoding.
94838view06:36, 6 October 2017Fehrhartfixed weird label
94307view11:36, 1 September 2017Marvin M2Connected unconnected lines
94221view22:26, 25 August 2017DeSlannotated metabolite nodes, connected unconnected lines.
94087view13:01, 18 August 2017DeSlConnectes lines to nodes.
93238view12:28, 7 August 2017Nasim.bSanganiits updated with inflammatory response
93216view12:51, 4 August 2017Nasim.bSanganiunder construction
93186view14:29, 2 August 2017Nasim.bSanganiupdated with Inflammatory pathway
93156view14:25, 1 August 2017Nasim.bSanganiUpdated with ROS
93130view12:22, 31 July 2017Nasim.bSangani
93128view12:19, 31 July 2017Nasim.bSangani
92382view12:42, 31 May 2017FehrhartOntology Term : 'Rett syndrome' added !
92381view12:42, 31 May 2017FehrhartOntology Term : 'histone modification pathway' added !
92380view12:42, 31 May 2017FehrhartModified description
92379view12:29, 31 May 2017FehrhartNew pathway

External references


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NameTypeDatabase referenceComment
APOE4 ProteinENSG00000130203 (Ensembl) 1)ApoE4 induced HDAC6-BDNF promoter IV binding, which reduced BDNF exon IV expression. ApoE4 induces translocation of HDAC4 and HDAC6 to the nucleus in primary human neurons and SH-SY5Y cells. Hypothesis: Nuclear translocation of HDAC6 is incresed which in turn reduces the expression of BDNF.

2)the e4 allele of APOE may serve as a candidate modulation factor for the Rett syndrome phenotype.

  1. this indicate a potential assocciation between cholestrol dyshomeostasis and RTT.
Alpha tubulin ProteinIPR002452 (InterPro)
Alpha tubulinProteinIPR002452 (InterPro)
CholesterolMetaboliteCHEBI:16113 (ChEBI)
FOXO3 Proteinacetylation of FOXO3 aatenuates its transcriptional activity
FOXO3ProteinENSG00000118689 (Ensembl) 1)FOXO3 positivey regulates HDAC6 as its downstream target. FOXO3 and HDAC6 have important implications in muscle atrophy. 2)MeCP2 KO mice have increased acetylated FOXO3.
HDAC3ProteinENSG00000171720 (Ensembl)
HDAC6ProteinENSG00000123358 (Ensembl) MeCP2 and HDAC6 commonly modulates the activation of the STAT3 pathway interestingly by reducing STAT3 phosphorylation of Tyr705. in the absence of HDAC6, STAT3 pathway is inactivated. HDAC6 is absolutely nesseccary for for the phosphorylation of STAT3.
MECP2ProteinENSG00000169057 (Ensembl)
NADMetaboliteCHEBI:13389 (ChEBI)
NADHMetaboliteHMDB01487 (HMDB)
NADPMetaboliteCHEBI:44409 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NOX2 (NADPH Oxidase)ProteinENSG00000165168 (Ensembl) 1)There is a positive feedback loop between HDAC6, NOX2-based NADPH oxidase, and ROS in astrocytes.Indeed, ROS AND NADPH oxidase can affect HDAC6 expression (THROUGH Uubiquitin binding domain) vice versa. (from Youn, at al, 2017) 2)HDAC6 overexpression induced ROS generation via upregulation of NADPH oxidase expression and activity. Indeed HDAC6 is an important regulator of ROS generation.
NR4A1ProteinENSG00000123358 (Ensembl) 1) it is an interactors of HDAC6 (BioGrid), however the source is not clearly explain the interaction.

2) It's among the differintially expressed gene list.(towards more downregulation). 3)Using HDACi induce its expression.Hypothesis:HDAC6 negatively regulates NR4A1.

4)Its dysregulation assocciated with neurological phenotype.e.g.Activity induced NR4A1 regulates spine density.
PKC zeta ProteinENSG00000067606 (Ensembl) 1)There is a positive feedback loop between NADPH-oxidase generated ROS and PKC- ZETA 2)PKC-ZETA inhibitor can almost abolsih ROS generation in cultured rat astrocyte.
ROSMetabolite26523 (ChEBI)
SOCS5GeneProductENSG00000171150 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl) MeCP2-miR-124-SOCS5 axis was cruicial for the activation of STAT3 in both neuronal and immune cell types.Indeed, loss of MeCP2 attenuate STAT3 activation in human astrocytes. Loss of MeCP2 reduces the IL-2 dependent phosphorylation of Tyr705 of STAT3, the hallmark of STAT3 activation.

Mechanism: Loss of MeCP2 in T cells impaaired the expression of microRNA (miR) miR-124, and consequently releived miR-124 mediated repression of the translation supressor SOSC5 mRNA. The resulting accumulation of SOCS5 led to inhibition SOCS5 dependent actvation of STAT3.

STAT3 Role in Microtubule:

STAT3 expression promote MT formation and increased the level of acetylated microtubules, it indeed stabilize MT structure.However, Our study supports this, as the pelleting of polymerized tubulin does not bring down Stat3. In addition, there was no obvious change in total tubulin protein or mRNA levels. This suggests that Stat3 does not directly modulate MT stability or tubulin expression. In contrast, our study indicates that Stat3 binds the COOH-terminal tubulin-binding domain of stathmin, which is thought to contribute significantly, although not solely, to its MT-destabilizing .This suggests that Stat3 may compete for the tubulin-binding site to antagonize the MT-desta bilizing activity of stathmin. In deed, STAT3 regulates MT dynamics through sequestration of the MT depolymerizing protein stathmin.

STAT3 Exerts Its Effect on MT via Stathmin, STAT3 interacts with stathmin and regulates MT dynamics by antagonizing its depolymerization activity
TAL1ProteinENSG00000162367 (Ensembl) No interaction was detected. According to encode database TAL1 is a promoter element of HDAC6.
TDP-43ProteinENSG00000120948 (Ensembl) TDP-43 positively regulates HDAC6. there are more literature available.
mRNA Processing Pathwaywp411 (WikiPathways)
miR-124RnaMIMAT0000134 (miRBase Sequence)

Annotated Interactions

No annotated interactions

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