期刊
CELL CHEMICAL BIOLOGY
卷 29, 期 7, 页码 1162-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2022.05.008
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Histone deacetylase (HDAC) proteins, known as epigenetic regulators, have emerged as anti-cancer therapeutics. This study demonstrates for the first time that HDAC4, HDAC5, and HDAC7 have reader functions, as they dissociate from corepressor NCoR in the presence of an acetyllysine-containing peptide. Mutation of a critical acetylation site regulates androgen receptor transcriptional activation through HDAC7-NCoR-HDAC3 dissociation.
Histone deacetylase (HDAC) proteins are epigenetic regulators that govern a wide variety of cellular events. With a role in cancer formation, HDAC inhibitors have emerged as anti-cancer therapeutics. Among the eleven metal-dependent class I, II, and IV HDAC proteins targeted by inhibitor drugs, class IIa HDAC4,-5,-7, and-9 harbor low deacetylase activity and are hypothesized to be readerproteins, which bind to post-translationally acetylated lysine. However, evidence linking acetyllysine binding to a downstream func-tional event is lacking. Here, we report for the first time that HDAC4,-5, and-7 dissociated from corepressor NCoR in the presence of an acetyllysine-containing peptide, consistent with reader function. Documenting the biological consequences of this possible reader function, mutation of a critical acetylation site regulated androgen receptor (AR) transcriptional activation function through HDAC7-NCoR-HDAC3 dissociation. The data document the first evidence consistent with epigenetic-reader functions of class IIa HDAC proteins.
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