Histone Deacetylases pp 85-94

Part of the Methods in Molecular Biology book series (MIMB, volume 1436)

Analysis of Expression and Functions of Histone Deacetylase 6 (HDAC6)

Protocol

Abstract

Histone deacetylase 6 (HDAC6) is a member of class IIb HDAC family. HDAC6 exists predominantly in the cytoplasm and deacetylates mainly non-histone proteins in the cytoplasm. Via its deacetylase and ubiquitin binding domains, HDAC6 regulates microtubules, cytoskeleton, intracellular trafficking, and cellular responses to stress. HDAC6 plays a central role in physiology and pathobiology in various organs and tissues. Herein we describe the methods for analysis of expression and function of HDAC6 in diverse physiological and pathological contexts.

Key words

Histone deacetylase 6 Acetylation Stress Chaperone Ubiquitin 

References

  1. 1.
    Bertos NR, Wang AH, Yang XJ (2001) Class II histone deacetylases: structure, function, and regulation. Biochem Cell Biol 79(3):243–252CrossRefPubMedGoogle Scholar
  2. 2.
    Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM et al (2002) The human genome browser at UCSC. Genome Res 12(6):996–1006. doi:10.1101/gr.229102, Article published online before print in May 2002CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Zhuang Y, Nguyen HT, Lasky JA, Cao S, Li C, Hu J et al (2010) Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-beta1-mediated gene activation. Biochem Biophys Res Commun 392(4):608–613. doi:10.1016/j.bbrc.2010.01.091 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bertos NR, Gilquin B, Chan GK, Yen TJ, Khochbin S, Yang XJ (2004) Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. J Biol Chem 279(46):48246–48254. doi:10.1074/jbc.M408583200, M408583200 [pii]CrossRefPubMedGoogle Scholar
  5. 5.
    Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W et al (2014) HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSalpha. Mol Cell 55(1):31–46. doi:10.1016/j.molcel.2014.04.028 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Grozinger CM, Hassig CA, Schreiber SL (1999) Three proteins define a class of human histone deacetylases related to yeast Hda1p. Proc Natl Acad Sci U S A 96(9):4868–4873CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Haggarty SJ, Koeller KM, Wong JC, Grozinger CM, Schreiber SL (2003) Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci U S A 100(8):4389–4394. doi:10.1073/pnas.0430973100 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A et al (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417(6887):455–458. doi:10.1038/417455a CrossRefPubMedGoogle Scholar
  9. 9.
    Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J et al (2007) HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell 27(2):197–213. doi:10.1016/j.molcel.2007.05.033 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV et al (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18(5):601–607. doi:10.1016/j.molcel.2005.04.021 CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang Y, Gilquin B, Khochbin S, Matthias P (2006) Two catalytic domains are required for protein deacetylation. J Biol Chem 281(5):2401–2404. doi:10.1074/jbc.C500241200 CrossRefPubMedGoogle Scholar
  12. 12.
    Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D et al (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A 101(16):6062–6067. doi:10.1073/pnas.0400782101 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Saji S, Kawakami M, Hayashi S, Yoshida N, Hirose M, Horiguchi S et al (2005) Significance of HDAC6 regulation via estrogen signaling for cell motility and prognosis in estrogen receptor-positive breast cancer. Oncogene 24(28):4531–4539. doi:10.1038/sj.onc.1208646 CrossRefPubMedGoogle Scholar
  14. 14.
    Lee YS, Lim KH, Guo X, Kawaguchi Y, Gao Y, Barrientos T et al (2008) The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis. Cancer Res 68(18):7561–7569. doi:10.1158/0008-5472.CAN-08-0188 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Akare S, Jean-Louis S, Chen W, Wood DJ, Powell AA, Martinez JD (2006) Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence. Int J Cancer 119(12):2958–2969. doi:10.1002/ijc.22231 CrossRefPubMedGoogle Scholar
  16. 16.
    Cabrero JR, Serrador JM, Barreiro O, Mittelbrunn M, Naranjo-Suarez S, Martin-Cofreces N et al (2006) Lymphocyte chemotaxis is regulated by histone deacetylase 6, independently of its deacetylase activity. Mol Biol Cell 17(8):3435–3445. doi:10.1091/mbc.E06-01-0008, E06-01-0008 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (2007) HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 129(7):1351–1363. doi:10.1016/j.cell.2007.04.035 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lam HC, Cloonan SM, Bhashyam AR, Haspel JA, Singh A, Sathirapongsasuti JF et al (2013) Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction. J Clin Invest 123(12):5212–5230. doi:10.1172/JCI69636 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ai J, Wang Y, Dar JA, Liu J, Liu L, Nelson JB et al (2009) HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer. Mol Endocrinol 23(12):1963–1972. doi:10.1210/me.2009-0188 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Parmigiani RB, Xu WS, Venta-Perez G, Erdjument-Bromage H, Yaneva M, Tempst P et al (2008) HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci U S A 105(28):9633–9638. doi:10.1073/pnas.0803749105 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP (2003) The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115(6):727–738CrossRefPubMedGoogle Scholar
  22. 22.
    Kwon S, Zhang Y, Matthias P (2007) The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev 21(24):3381–3394. doi:10.1101/gad.461107 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Iwata A, Riley BE, Johnston JA, Kopito RR (2005) HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem 280(48):40282–40292. doi:10.1074/jbc.M508786200 CrossRefPubMedGoogle Scholar
  24. 24.
    Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB et al (2007) HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447(7146):859–863. doi:10.1038/nature05853 CrossRefPubMedGoogle Scholar
  25. 25.
    Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS et al (2010) HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J 29(5):969–980. doi:10.1038/emboj.2009.405 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Edmond V, Moysan E, Khochbin S, Matthias P, Brambilla C, Brambilla E et al (2011) Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin. EMBO J 30(3):510–523. doi:10.1038/emboj.2010.333 CrossRefPubMedGoogle Scholar
  27. 27.
    Chaudhary N, Nakka KK, Chavali PL, Bhat J, Chatterjee S, Chattopadhyay S (2014) SMAR1 coordinates HDAC6-induced deacetylation of Ku70 and dictates cell fate upon irradiation. Cell Death Dis 5:e1447. doi:10.1038/cddis.2014.397 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Pathogen Biology, College of Basic Medical SciencesChina Medical UniversityShenyangPeople’s Republic of China
  2. 2.Department of MedicineTulane University School of MedicineNew OrleansUSA
  3. 3.College of Medical SciencesWashington State University at SpokaneSpokaneUSA

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