Nonhistone protein acetylation as cancer therapy targets

Brahma N. Singh, Guanghua Zhang, Yi L. Hwa, Jinping Li, Sean Christopher Dowdy, Shi Wen Jiang

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)935-954
Number of pages20
JournalExpert Review of Anticancer Therapy
Volume10
Issue number6
DOIs
StatePublished - Jun 2010

Fingerprint

Acetylation
Histone Deacetylases
Neoplasms
Proteins
Therapeutics
Histones
Histone Acetyltransferases
Histone Deacetylase Inhibitors
Oncogene Proteins
RNA Stability
Post Translational Protein Processing
Tumor Suppressor Genes
Proteolysis
Genes
Lysine
Chromatin
Carcinogenesis
Cell Proliferation
Apoptosis
Neoplasm Metastasis

Keywords

  • Acetylation
  • Cancer therapy
  • Deacetylation
  • Epigenetics
  • HDAC
  • HDAC inhibitor
  • Histone deacetylase
  • Nonhistone acetylation

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Oncology

Cite this

Nonhistone protein acetylation as cancer therapy targets. / Singh, Brahma N.; Zhang, Guanghua; Hwa, Yi L.; Li, Jinping; Dowdy, Sean Christopher; Jiang, Shi Wen.

In: Expert Review of Anticancer Therapy, Vol. 10, No. 6, 06.2010, p. 935-954.

Research output: Contribution to journalArticle

Singh, Brahma N. ; Zhang, Guanghua ; Hwa, Yi L. ; Li, Jinping ; Dowdy, Sean Christopher ; Jiang, Shi Wen. / Nonhistone protein acetylation as cancer therapy targets. In: Expert Review of Anticancer Therapy. 2010 ; Vol. 10, No. 6. pp. 935-954.
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