GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:12606581

From GONUTS
Jump to: navigation, search
Citation

Zhang, Y, Li, N, Caron, C, Matthias, G, Hess, D, Khochbin, S and Matthias, P (2003) HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J. 22:1168-79

Abstract

Microtubules are cylindrical cytoskeletal structures found in almost all eukaryotic cell types which are involved in a great variety of cellular processes. Reversible acetylation on the epsilon-amino group of alpha-tubulin Lys40 marks stabilized microtubule structures and may contribute to regulating microtubule dynamics. Yet, the enzymes catalysing this acetylation/deacetylation have remained unidentified until recently. Here we report that beta-tubulin interacts with histone deacetylase-6 (HDAC-6) in a yeast two-hybrid assay and in vitro. We find that HDAC-6 is a micro tubule-associated protein capable of deacetylating alpha-tubulin in vivo and in vitro. HDAC-6's microtubule binding and deacetylation functions both depend on the hdac domains. Overexpression of HDAC-6 in mammalian cells leads to tubulin hypoacetylation. In contrast, inhibition of HDAC-6 function by two independent mechanisms--pharmacological (HDAC inhibitors) or genetic (targeted inactivation of HDAC-6 in embryonic stem cells)--leads to hyperacetylation of tubulin and microtubules. Taken together, our data provide evidence that HDAC-6 might act as a dual deacetylase for tubulin and histones, and suggest the possibility that acetylated non-histone proteins might represent novel targets for pharmacological therapy by HDAC inhibitors.

Links

PubMed PMC150348 Online version:10.1093/emboj/cdg115

Keywords

3T3 Cells; Acetylation; Animals; Cattle; Chromatography, High Pressure Liquid; Embryo, Mammalian/anatomy & histology; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Humans; Kidney/cytology; Mice; Microtubules/metabolism; Paclitaxel/metabolism; Peptides/chemistry; Peptides/metabolism; Protein Binding; Protein Structure, Tertiary; Stem Cells/cytology; Stem Cells/metabolism; Tubulin/chemistry; Tubulin/metabolism; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HDAC6

part_of

GO:0015630: microtubule cytoskeleton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HDAC6

colocalizes_with

GO:0005881: cytoplasmic microtubule

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HDAC6

enables

GO:0042903: tubulin deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:HDAC6

enables

GO:0048487: beta-tubulin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:HDAC6

acts_upstream_of_or_within

GO:0090042: tubulin deacetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.