HDAC6 interactions in the central nervous system (WP5426)

Homo sapiens

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HDAC6 stands out as a distinctive member within the histone deacetylase family due to its predominant presence in the cytosol, facilitating its interaction with a wide array of non-histone proteins. Its dysregulation has been linked to various outcomes, encompassing diverse cancer types, immune-related disorders, and neurological conditions, including Alzheimer's, Parkinson's, ALS, Huntington's, Charcot-Marie-Tooth disease, and Rett syndrome. The current network represents the known HDAC6 interactions in the central nervous system (CNS).

Authors

NasimBahramSangani , Alex Pico , Kristina Hanspers , and Egon Willighagen

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

regulatory pathway pertinent to the brain

Participants
Query Drugst.One

Label Type Compact URI Comment
MYH9 GeneProduct ensembl:ENSG00000100345
TUBA4A GeneProduct ensembl:ENSG00000127824
BIRC5 GeneProduct ensembl:ENSG00000089685
VCP GeneProduct ensembl:ENSG00000165280
tat GeneProduct ncbigene:155871
GSK3A GeneProduct ensembl:ENSG00000105723
NR3C1 GeneProduct ensembl:ENSG00000113580
MYD88 GeneProduct ensembl:ENSG00000172936
HSPA8 GeneProduct ensembl:ENSG00000109971
KALRN GeneProduct ensembl:ENSG00000160145
SEPTIN7 GeneProduct ensembl:ENSG00000122545 
POU5F1 GeneProduct ensembl:ENSG00000204531
OPTN GeneProduct ensembl:ENSG00000123240
PARK7 GeneProduct ensembl:ENSG00000116288
NR3C1 GeneProduct ensembl:ENSG00000113580
MAPRE1 GeneProduct ensembl:ENSG00000101367
MIIP GeneProduct ensembl:ENSG00000116691
ACTR1A GeneProduct ensembl:ENSG00000138107
PXN GeneProduct ensembl:ENSG00000089159
TWIST1 GeneProduct ensembl:ENSG00000122691
CYBB GeneProduct ensembl:ENSG00000165168
STUB1 GeneProduct ensembl:ENSG00000103266
ATXN3 GeneProduct ensembl:ENSG00000066427 Burnett et al. also found that ataxin-3 interacts with HDAC6 and dynein motor
HDAC6 GeneProduct ensembl:ENSG00000094631 Type your comment here
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BDNF GeneProduct ensembl:ENSG00000176697 Type your comment here
APOE GeneProduct ensembl:ENSG00000130203 Type your comment here
BBIP1 GeneProduct ensembl:ENSG00000214413
MAPT GeneProduct ensembl:ENSG00000186868
HDAC11 GeneProduct ensembl:ENSG00000163517
ERG GeneProduct ensembl:ENSG00000157554
HDAC9 GeneProduct ensembl:ENSG00000048052
SQSTM1 GeneProduct ensembl:ENSG00000161011
TRIM50 None
UBD GeneProduct ensembl:ENSG00000213886
G3BP1 GeneProduct ensembl:ENSG00000145907
TPPP GeneProduct ensembl:ENSG00000171368
PRKCE GeneProduct ensembl:ENSG00000171132
SMAD2 GeneProduct ensembl:ENSG00000175387
PROM1 GeneProduct ensembl:ENSG00000007062
RAD23B GeneProduct ensembl:ENSG00000119318
AKT1 GeneProduct ensembl:ENSG00000142208
CFTR GeneProduct ensembl:ENSG00000001626
ISG15 GeneProduct ensembl:ENSG00000187608
EP300 GeneProduct ensembl:ENSG00000100393
SOD1 GeneProduct ensembl:ENSG00000142168
GRK2 GeneProduct ensembl:ENSG00000173020
GSK3B GeneProduct ensembl:ENSG00000082701 GSK3b was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3b resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3b phosphorylation site in HDAC6.. We also provide evidence that GSK3b may directly regulate HDAC6.
PRKCZ GeneProduct ensembl:ENSG00000067606
EGFR GeneProduct ensembl:ENSG00000146648
AURKA GeneProduct ensembl:ENSG00000087586 AurA phosphorylates HDAC6 to activate
MAPK3 GeneProduct ensembl:ENSG00000102882
MAPK1 GeneProduct ensembl:ENSG00000100030
SIRT2 GeneProduct ensembl:ENSG00000068903
HDAC6 GeneProduct ensembl:ENSG00000094631
HDAC6 GeneProduct ensembl:ENSG00000094631
CDC20 GeneProduct ensembl:ENSG00000117399
HDAC11 GeneProduct ensembl:ENSG00000163517
HSP90AA1 GeneProduct ensembl:ENSG00000080824
HSF1 GeneProduct ensembl:ENSG00000185122
HDAC6 GeneProduct ensembl:ENSG00000094631
CTNNB1 GeneProduct ensembl:ENSG00000168036
PROM1 GeneProduct ensembl:ENSG00000007062
HDAC6 GeneProduct ensembl:ENSG00000094631
ELP1 GeneProduct ensembl:ENSG00000070061
MAPK8 GeneProduct ensembl:ENSG00000107643
HDAC6 GeneProduct ensembl:ENSG00000094631
EP400 GeneProduct ensembl:ENSG00000183495
KAT5 GeneProduct ensembl:ENSG00000172977
HDAC6 GeneProduct ensembl:ENSG00000094631
SMAD2 GeneProduct ensembl:ENSG00000175387
CDC20 GeneProduct ensembl:ENSG00000117399
APC GeneProduct ensembl:ENSG00000134982
CDC20 GeneProduct ensembl:ENSG00000117399
RAC1 GeneProduct ensembl:ENSG00000136238
DLG4 GeneProduct ensembl:ENSG00000132535
DLG2 GeneProduct ensembl:ENSG00000150672
SNCAIP GeneProduct ensembl:ENSG00000064692
HTT GeneProduct ensembl:ENSG00000197386
ELP3 GeneProduct ensembl:ENSG00000134014
PPP1CA GeneProduct ensembl:ENSG00000172531
HDAC6 GeneProduct ensembl:ENSG00000094631
SGK3 GeneProduct ensembl:ENSG00000104205
SGK1 GeneProduct ensembl:ENSG00000118515
MAP1LC3A GeneProduct ensembl:ENSG00000101460 Type your comment here
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NEDD9 GeneProduct ensembl:ENSG00000111859
HDAC6 GeneProduct ensembl:ENSG00000094631
HDAC6 GeneProduct ensembl:ENSG00000094631
CSNK2B GeneProduct ensembl:ENSG00000204435 To verify the association of HDAC6 with CK2, we performed a pull-down assay using two recombinant proteins (GST–HDAC6 and CK2 holoenzyme) and individual subunit proteins (Fig. 2C, top). Only CK2 holoenzyme was found to be associated with HDAC6, whereas CK2α and CK2β alone failed to precipitate with HDAC6, indicating that the CK2 holoenzyme associates with HDAC6
DCTN1 GeneProduct ensembl:ENSG00000204843
GRIA2 GeneProduct ensembl:ENSG00000120251
GRIA1 GeneProduct ensembl:ENSG00000155511
TARDBP GeneProduct ensembl:ENSG00000120948
FUS GeneProduct ensembl:ENSG00000089280
DYNC1I2 GeneProduct ensembl:ENSG00000077380
HDAC6 GeneProduct ensembl:ENSG00000094631
HDAC6 GeneProduct ensembl:ENSG00000094631
MAPT GeneProduct ensembl:ENSG00000186868
CSNK2A2 GeneProduct ensembl:ENSG00000070770 To verify the association of HDAC6 with CK2, we performed a pull-down assay using two recombinant proteins (GST–HDAC6 and CK2 holoenzyme) and individual subunit proteins (Fig. 2C, top). Only CK2 holoenzyme was found to be associated with HDAC6, whereas CK2α and CK2β alone failed to precipitate with HDAC6, indicating that the CK2 holoenzyme associates with HDAC6
HSPA8 GeneProduct ensembl:ENSG00000109971
SP1 GeneProduct ensembl:ENSG00000185591
FOXP3 GeneProduct ensembl:ENSG00000049768
CCDC141 GeneProduct ensembl:ENSG00000163492
HIF1A GeneProduct ensembl:ENSG00000100644
PRKN GeneProduct ensembl:ENSG00000185345
GARS1 GeneProduct ensembl:ENSG00000106105 Interestingly, pulldown experiments showed that HDAC6 can co-immunoprecipitate with HSPB1 (CMT2E) (Zhang et al., 2007), but also with GlyRS (CMT2D)
HSPB1 GeneProduct ensembl:ENSG00000106211
CTTN GeneProduct ensembl:ENSG00000085733
CTNNB1 GeneProduct ensembl:ENSG00000168036
XRCC6 GeneProduct ensembl:ENSG00000196419
PRDX1 GeneProduct ensembl:ENSG00000117450
PRDX2 GeneProduct ensembl:ENSG00000167815
DNAJA1 GeneProduct ensembl:ENSG00000086061 Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity
HSP90AA1 GeneProduct ensembl:ENSG00000080824
TUBB GeneProduct ensembl:ENSG00000196230
TUBB3 GeneProduct ensembl:ENSG00000258947
TUBA1C GeneProduct ensembl:ENSG00000167553
TUBA3C GeneProduct ensembl:ENSG00000198033
SMAD7 GeneProduct ensembl:ENSG00000101665 Silencing HDAC6 increased SMAD7 protein expression
tat GeneProduct uniprot:155871
TUBA4A GeneProduct ensembl:ENSG00000127824
HDAC6 GeneProduct ensembl:ENSG00000094631
PRKCZ GeneProduct ensembl:ENSG00000067606 Type your comment here
MAPT GeneProduct ensembl:ENSG00000186868
HDAC6 GeneProduct ensembl:ENSG00000094631
PRKN GeneProduct ensembl:ENSG00000185345
HSP90AA1 GeneProduct ensembl:ENSG00000080824
HSF1 GeneProduct ensembl:ENSG00000185122
HDAC6 GeneProduct ensembl:ENSG00000094631
HDAC6 GeneProduct ensembl:ENSG00000094631 Type your comment here
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HDAC6 GeneProduct ensembl:ENSG00000094631 Type your comment here
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HDAC6 GeneProduct ensembl:ENSG00000094631 Type your comment here
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HDAC6 GeneProduct ensembl:ENSG00000094631 Type your comment here
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HDAC6 GeneProduct ensembl:ENSG00000094631 Type your comment here
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APC GeneProduct ensembl:ENSG00000134982
XRCC6 GeneProduct ensembl:ENSG00000196419
BAX GeneProduct ensembl:ENSG00000087088
VHL GeneProduct ensembl:ENSG00000134086
HDAC6 GeneProduct ensembl:ENSG00000094631
VHL GeneProduct ensembl:ENSG00000134086
KALRN GeneProduct ensembl:ENSG00000160145
SQSTM1 GeneProduct ensembl:ENSG00000161011
BCL2 GeneProduct ensembl:ENSG00000171791
BAX GeneProduct ensembl:ENSG00000087088
VIM Protein ensembl:ENSG00000026025
MAP1B Protein ensembl:ENSG00000131711
SHH Protein ensembl:ENSG00000164690
HSPA4 Protein ensembl:ENSG00000170606
ITIH4 Protein ensembl:ENSG00000055955
PTK2B Protein ensembl:ENSG00000120899
MAP3K5 Protein ensembl:ENSG00000197442
SNCA Protein ensembl:ENSG00000145335
ATP13A2 Protein ensembl:ENSG00000159363
ARID3A Protein ensembl:ENSG00000116017
HSPA4 Protein ensembl:ENSG00000170606
MDH1 Protein ensembl:ENSG00000014641
NDUFV1 Protein ensembl:ENSG00000167792
MIF Protein ensembl:ENSG00000240972
RHOT1 Protein ensembl:ENSG00000126858
CNOT6 Protein ensembl:ENSG00000113300

References

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  49. Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation. Ageta-Ishihara N, Miyata T, Ohshima C, Watanabe M, Sato Y, Hamamura Y, et al. Nat Commun. 2013;4:2532. PubMed Europe PMC Scholia
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  52. Primary cilia in stem cells and neural progenitors are regulated by neutral sphingomyelinase 2 and ceramide. He Q, Wang G, Wakade S, Dasgupta S, Dinkins M, Kong JN, et al. Mol Biol Cell. 2014 Jun;25(11):1715–29. PubMed Europe PMC Scholia
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  54. Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells. Cheng F, Lienlaf M, Perez-Villarroel P, Wang HW, Lee C, Woan K, et al. Mol Immunol. 2014 Jul;60(1):44–53. PubMed Europe PMC Scholia
  55. HDAC6 is a Bruchpilot deacetylase that facilitates neurotransmitter release. Miskiewicz K, Jose LE, Yeshaw WM, Valadas JS, Swerts J, Munck S, et al. Cell Rep. 2014 Jul 10;8(1):94–102. PubMed Europe PMC Scholia
  56. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Falkenberg KJ, Johnstone RW. Nat Rev Drug Discov. 2014 Sep;13(9):673–91. PubMed Europe PMC Scholia
  57. Tubulin acetylation promoting potency and absorption efficacy of deacetylase inhibitors. Mangas-Sanjuan V, Oláh J, Gonzalez-Alvarez I, Lehotzky A, Tőkési N, Bermejo M, et al. Br J Pharmacol. 2015 Feb;172(3):829–40. PubMed Europe PMC Scholia
  58. Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity. Zhang L, Liu S, Liu N, Zhang Y, Liu M, Li D, et al. Protein Cell. 2015 Jan;6(1):42–54. PubMed Europe PMC Scholia
  59. Interferon-stimulated gene 15 (ISG15) and ISG15-linked proteins can associate with members of the selective autophagic process, histone deacetylase 6 (HDAC6) and SQSTM1/p62. Nakashima H, Nguyen T, Goins WF, Chiocca EA. J Biol Chem. 2015 Jan 16;290(3):1485–95. PubMed Europe PMC Scholia
  60. Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway. Dhanyamraju PK, Holz PS, Finkernagel F, Fendrich V, Lauth M. Mol Cancer Ther. 2015 Mar;14(3):727–39. PubMed Europe PMC Scholia
  61. aPKC phosphorylation of HDAC6 results in increased deacetylation activity. Du Y, Seibenhener ML, Yan J, Jiang J, Wooten MC. PLoS One. 2015 Apr 10;10(4):e0123191. PubMed Europe PMC Scholia
  62. Novel Interaction of Class IIb Histone Deacetylase 6 (HDAC6) with Class IIa HDAC9 Controls Gonadotropin Releasing Hormone (GnRH) Neuronal Cell Survival and Movement. Salian-Mehta S, Xu M, McKinsey TA, Tobet S, Wierman ME. J Biol Chem. 2015 May 29;290(22):14045–56. PubMed Europe PMC Scholia
  63. ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation. Sen A, Nelson TJ, Alkon DL. J Neurosci. 2015 May 13;35(19):7538–51. PubMed Europe PMC Scholia
  64. HDAC6 mediates HIV-1 tat-induced proinflammatory responses by regulating MAPK-NF-kappaB/AP-1 pathways in astrocytes. Youn GS, Ju SM, Choi SY, Park J. Glia. 2015 Nov;63(11):1953–65. PubMed Europe PMC Scholia
  65. Histone deacetylase 6 promotes growth of glioblastoma through inhibition of SMAD2 signaling. Li S, Liu X, Chen X, Zhang L, Wang X. Tumour Biol. 2015 Dec;36(12):9661–5. PubMed Europe PMC Scholia
  66. HDAC6 Regulates the Chaperone-Mediated Autophagy to Prevent Oxidative Damage in Injured Neurons after Experimental Spinal Cord Injury. Su M, Guan H, Zhang F, Gao Y, Teng X, Yang W. Oxid Med Cell Longev. 2016;2016:7263736. PubMed Europe PMC Scholia
  67. SIRT2 inactivation reveals a subset of hyperacetylated perinuclear microtubules inaccessible to HDAC6. Skoge RH, Ziegler M. J Cell Sci. 2016 Aug 1;129(15):2972–82. PubMed Europe PMC Scholia
  68. Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice. Jianhua F, Wei W, Xiaomei L, Shao-Hui W. Behav Brain Res. 2017 Jan 1;316:136–44. PubMed Europe PMC Scholia
  69. Rescue of CAMDI deletion-induced delayed radial migration and psychiatric behaviors by HDAC6 inhibitor. Fukuda T, Nagashima S, Abe T, Kiyonari H, Inatome R, Yanagi S. EMBO Rep. 2016 Dec;17(12):1785–98. PubMed Europe PMC Scholia
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