Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization.

By C. Grozinger, Stefan Schreiber. Proceedings of the National Academy of Sciences of the United States of America, 2000

640 citations recorded by the source corpus.

Transcription is controlled in part by the dynamic acetylation and deacetylation of histone proteins. The latter process is mediated by histone deacetylases (HDACs). Previous analysis of the regulation of HDAC activity in transcription has focused primarily on the recruitment of HDAC proteins to specific promoters or chromosomal domains by association with DNA-binding proteins. To characterize the cellular function of the recently identified HDAC4 and HDAC5 proteins, complexes were isolated by immunoprecipitation. Both HDACs were found to interact with14-3-3 proteins at three phosphorylation sites. The association of 14-3-3 with HDAC4 and HDAC5 results in the sequestration of these proteins in the cytoplasm. Loss of this interaction allows HDAC4 and HDAC5 to translocate to the nucleus, interact with HDAC3, and repress gene expression. Regulation of the cellular localization of HDAC4 and HDAC5 by 14-3-3 represents a mechanism for controlling the transcriptional activity of these class II HDAC proteins.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0787095355b9efb3197addc69fd9b3b1c2a67ec1

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In Molecular Biology

1. E. Olson
2. Xiang-Jiao Yang
3. E. Seto
4. J. Richardson
5. Joseph A. Hill
6. PA Marks
7. Michael B. Yaffe
8. T. McKinsey

Citations in the corpus

• Therapeutic application of histone deacetylase inhibitors for central nervous system disorders (2008, background): “Retention in the cytoplasm is controlled by 14-3-3 anchor proteins, which bind exclusively to the phosphorylated from of HDACs and prevent entry into the nucleus, whereas nuclear re-entry occurs upon protein dephosphorylatio”
• The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men (2008, background): “Indeed, affinity purification of mammalian class IIa HDACs identified 14-3-3 protein”
• Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets (2015, background): “Nucleo-cytoplasmic shuttling is a key mechanism regulating class IIa HDAC function (Grozinger and Schreiber 2000; Harrison et al. 2004; McKinsey et al. 2000a; Vega et al. 2004).”
• Histone Deacetylases 5 and 9 Govern Responsiveness of the Heart to a Subset of Stress Signals and Play Redundant Roles in Heart Development (2004, background): “Signal-dependent phosphorylation of class II HDACs creates binding sites for 14-3-3 chaperone proteins, which mediate their translocation from the nucleus to the cytoplasm and consequent derepression of the hypertrophic gene program (9, 27, 28).”
• Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. (2004, background): “…HDACs by calcium/calmodulin-dependent kinaseBaylor College of Medicine (CaMK), and other kinases, in response to specific stim-One Baylor Plaza uli creates docking sites for the 14-3-3 family of proteinHouston, Texas 77030 chaperones (Grozinger and Schreiber, 2000; McKinsey et al., 2000a, 2000b).”
• Analysis of histone acetyltransferase and histone deacetylase families of Arabidopsis thaliana suggests functional diversification of chromatin modification among multicellular eukaryotes. (2002, background): “Similar nuclear export signals in human and mouse class II proteins are known to be involved in shuttling these proteins between an active state in the nucleus and an inactive, phosphorylated state in the cytoplasm (62,63).”
• The SMRT and N-CoR Corepressors Are Activating Cofactors for Histone Deacetylase 3 (2001, background): “Although class II HDACs can be regulated by subcellular localization ( 13 , 36, 37, 59), they are also inactive when expressed recombinantly and thus may require one or more activating subunits as an additional layer of regulatory control.”
• TAZ: a novel transcriptional co‐activator regulated by interactions with 14‐3‐3 and PDZ domain proteins (2000, background): “, 1998), histone acetyltransferase (Imhof and Wolffe, 1999) and histone deacetylase (Grozinger and Schreiber, 2000).”