In:
PROTEOMICS, Wiley, Vol. 14, No. 19 ( 2014-10), p. 2156-2166
Abstract:
Class IIa histone deacetylases ( HDAC s) are critical transcriptional regulators, shuttling between nuclear and cytoplasmic cellular compartments. Within the nucleus, these HDAC s repress transcription as components of multiprotein complexes, such as the nuclear corepressor and beclin‐6 corepressor ( BC o R ) complexes. Cytoplasmic relocalization relieves this transcriptional repressive function. Class IIa HDAC shuttling is controlled, in part, by phosphorylations flanking the nuclear localization signal ( NLS ). Furthermore, we have reported that phosphorylation within the NLS by the kinase A urora B modulates the localization and function of the class IIa HDAC 5 during mitosis. While we identified numerous additional HDAC 5 phosphorylations, their regulatory functions remain unknown. Here, we studied phosphorylation sites within functional HDAC 5 domains, including the deacetylation domain ( DAC , Ser755), nuclear export signal ( NES , Ser1108), and an acidic domain ( AD , Ser611). We have generated phosphomutant cell lines to investigate how absence of phosphorylation at these sites impacts HDAC 5 localization, enzymatic activity, and protein interactions. Combining molecular biology and quantitative MS , we have defined the interactions and HDAC 5‐containing complexes mediated by site‐specific phosphorylation and quantified selected changes using parallel reaction monitoring. These results expand the current understanding of HDAC regulation, and the functions of this critical family of proteins within human cells.
Type of Medium:
Online Resource
ISSN:
1615-9853
,
1615-9861
DOI:
10.1002/pmic.201400092
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2037674-1
SSG:
12
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