Skip to main content
SpringerLink
Log in

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

  • Protocol
  • First Online:
Histone Deacetylases

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

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bertos NR, Wang AH, Yang XJ (2001) Class II histone deacetylases: structure, function, and regulation. Biochem Cell Biol 79(3):243–252

    Article  CAS  PubMed  Google Scholar 

  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 2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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]

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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):4868–4873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):727–738

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, People’s Republic of China

    Miao Li

  2. Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA

    Yan Zhuang

  3. College of Medical Sciences, Washington State University at Spokane, 412 E Spokane Falls Blvd., Spokane, WA, 99202, USA

    Bin Shan

Authors
  1. Miao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Zhuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bin Shan .

Editor information

Editors and Affiliations

  1. Boston University School of Medicine, Boston, Massachusetts, USA

    Sibaji Sarkar

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Li, M., Zhuang, Y., Shan, B. (2016). Analysis of Expression and Functions of Histone Deacetylase 6 (HDAC6). In: Sarkar, S. (eds) Histone Deacetylases. Methods in Molecular Biology, vol 1436. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3667-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3667-0_6

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3665-6

  • Online ISBN: 978-1-4939-3667-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation