Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity

Zhang, Linlin; Liu, Shanshan; Liu, Ningning; Zhang, Yong; Liu, Min; Li, Dengwen; Seto, Edward; Yao, Tso‐Pang; Wang, Shui; Zhou, Jun

doi:10.1007/s13238-014-0102-8

Cited by 53 publications

(60 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of 24 new PTM sites, reported here, were not covered in previous global proteomic data sets. [11][12][13][14][15][16]32,33 A functional evaluation of tubulin mutants on specific phosphorylation and acetylation residues implied their distinct roles in the control of microtubule assembly and stability as well as the microtubule-dependent retrograde transport of adenoviruses.…”

Section: ■ Discussionmentioning

confidence: 99%

Proteomic Profiling and Functional Characterization of Multiple Post-Translational Modifications of Tubulin

et al. 2015

Self Cite

View full text Add to dashboard Cite

Tubulin is known to undergo unique post-translational modifications (PTMs), such as detyrosination and polyglutamylation, particularly in the unstructured carboxy-terminal tails (CTTs). However, more conventional PTMs of tubulin and their roles in the regulation of microtubule properties and functions remain poorly defined. Here, we report the comprehensive profiling of tubulin phosphorylation, acetylation, ubiquitylation, and O-GlcNAcylation in HeLa cells with a proteomic approach. Our tubulin-targeted analysis has identified 80 residues bearing single or multiple conventional PTMs including 24 novel PTM sites not covered in previous global proteomic surveys. By using a series of PTM-deficient or PTM-mimicking mutants, we further find that tubulin phosphorylation and acetylation play important roles in the control of microtubule assembly and stability. In addition, these tubulin PTMs have distinct effects on the retrograde transport of adenoviruses along microtubules. These findings thus enlarge the repertoire of tubulin PTMs and foster our understanding of their versatile roles in the regulation of microtubule dynamics and cellular functions.

show abstract

Section: ■ Discussionmentioning

confidence: 99%

Proteomic Profiling and Functional Characterization of Multiple Post-Translational Modifications of Tubulin

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…HDAC6 heterozygous (HZ) mice were obtained from Tso-Pang Yao (Duke University, Durham, NC, USA) and intercrossed to generate HDAC6 knockout (KO) and wild-type (WT) littermates as described previously 16, 17. Mice were maintained in a specific pathogen-free barrier facility.…”

Section: Methodsmentioning

confidence: 99%

HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies

Yan¹,

Liu²,

Hong³

et al. 2017

Theranostics

Self Cite

View full text Add to dashboard Cite

The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4+ or CD8+ T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4+ γδ T cells in the spleen and lymph nodes. Consistent with these observations, small-molecule inhibition of HDAC6 activity in γδ T cells promotes the expression of IL-17 in vitro. These data thus reveal that HDAC6 represses IL-17 production in T cells, providing novel insights into the role of HDAC6 in the immune system. These findings also have important implications for the clinical investigation of HDAC6-targeted therapies.

show abstract

“…Conversely, such robust chemical enrichment methods are not available for lysine modifications such as acetylation or malonylation, and their analysis usually requires antibody-based enrichment of the modified peptides after enzymatic digestion [32,33,34,35,36]. Alternatively, immunoprecipitation of intact proteins has been applied [37]. Taken together, these techniques use powerful, advanced sample preparation and MS approaches, which are available only in specialized laboratories.…”

Section: Introductionmentioning

confidence: 99%

Partial Immunoblotting of 2D-Gels: A Novel Method to Identify Post-Translationally Modified Proteins Exemplified for the Myelin Acetylome

et al. 2017

View full text Add to dashboard Cite

Post-translational modifications (PTMs) play a key role in regulating protein function, yet their identification is technically demanding. Here, we present a straightforward workflow to systematically identify post-translationally modified proteins based on two-dimensional gel electrophoresis. Upon colloidal Coomassie staining the proteins are partially transferred, and the investigated PTMs are immunodetected. This strategy allows tracking back the immunopositive antigens to the corresponding spots on the original gel, from which they are excised and mass spectrometrically identified. Candidate proteins are validated on the same membrane by immunodetection using a second fluorescence channel. We exemplify the power of partial immunoblotting with the identification of lysine-acetylated proteins in myelin, the oligodendroglial membrane that insulates neuronal axons. The excellent consistency of the detected fluorescence signals at all levels allows the differential comparison of PTMs across multiple conditions. Beyond PTM screening, our multi-level workflow can be readily adapted to clinical applications such as identifying auto-immune antigens or host-pathogen interactions.

show abstract

Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity

Cited by 53 publications

References 44 publications

Proteomic Profiling and Functional Characterization of Multiple Post-Translational Modifications of Tubulin

Proteomic Profiling and Functional Characterization of Multiple Post-Translational Modifications of Tubulin

HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies

Partial Immunoblotting of 2D-Gels: A Novel Method to Identify Post-Translationally Modified Proteins Exemplified for the Myelin Acetylome

Contact Info

Product

Resources

About