Nonhistone protein acetylation as cancer therapy targets.
Acetylation and deacetylation are counteracting, post-translational modifications that affect a large number of histone and nonhistone proteins. The significance of histone acetylation in the modification of chromatin structure and dynamics, and thereby gene transcription regulation, has been well recognized. A steadily growing number of nonhistone proteins have been identified as acetylation targets and reversible lysine acetylation in these proteins plays an important role(s) in the regulation of mRNA stability, protein localization and degradation, and protein-protein and protein-DNA interactions. The recruitment of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to the transcriptional machinery is a key element in the dynamic regulation of genes controlling cellular proliferation, differentiation and apoptosis. Many nonhistone proteins targeted by acetylation are the products of oncogenes or tumor-suppressor genes and are directly involved in tumorigenesis, tumor progression and metastasis. Aberrant activity of HDACs has been documented in several types of cancers and HDAC inhibitors (HDACi) have been employed for therapeutic purposes. Here we review the published literature in this field and provide updated information on the regulation and function of nonhistone protein acetylation. While concentrating on the molecular mechanism and pathways involved in the addition and removal of the acetyl moiety, therapeutic modalities of HDACi are also discussed.
Singh
Brahma N
BN
Department of Mycology & Plant Pathology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, India.
Zhang
Guanghua
G
Hwa
Yi L
YL
Li
Jinping
J
Dowdy
Sean C
SC
Jiang
Shi-Wen
SW
D000107:Acetylation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology
D002868:Chromosomal Proteins, Non-Histone; D056572:Histone Deacetylase Inhibitors