Please note: This annotation is based on BLASTn hit with very strong hits.

BLASTx of GenBank produced these top hits (although neither result is significant)

                                                                   Score     E
Sequences producing significant alignments:                       (Bits)  Value

gb|ACG24960.1|  histone deacetylase complex subunit SAP18 [Zea...  72.0    4e-11
ref|NP_001132841.1|  hypothetical protein LOC100194333 [Zea ma...  72.0    4e-11 

Sequences producing significant alignments:
(Click headers to sort columns)

Accession	Description	Max score	Total score	Query coverage	E value	Max ident	Links
EU965204.1	Zea mays clone 284465 histone deacetylase complex subunit SAP18 mRNA, complete cds	828	1016	83%	0.0	98%
EU952842.1	Zea mays clone 1290829 histone deacetylase complex subunit SAP18 mRNA, complete cds	556	556	48%	4e-155	97%

Literature:

Int J Oncol. 2008 Oct;33(4):637-46. Links

Histone deacetylase inhibitors: apoptotic effects and clinical implications (Review).

Emanuele S, Lauricella M, Tesoriere G.

Dipartimento di Scienze Biochimiche, Università di Palermo, Policlinico, I-90127 Palermo, Italy. s.emanuele@unipa.it

It has been shown that epigenetic modifications play an important role in tumorigenesis. Thus, affecting epigenetic tumorigenic alterations can represent a promising strategy for anticancer targeted therapy. Among the key chromatin modifying enzymes which influence gene expression, histone acetyltransferases (HATs) and histone deacetylases (HDACs) have recently attracted interest because of their impact on tumor development and progression. Increased expression of HDACs and disrupted activities of HATs have been found in several tumor types, with a consequent hypoacetylated state of chromatin that can be strictly correlated with low expression of either tumor suppressor or pro-apoptotic genes. Histone deacetylase inhibitors (HDACIs) represent a new and promising class of antitumor drugs that influence gene expression by enhancing acetylation of histones in specific chromatin domains. HDACIs have been shown to exert potent anticancer activities inducing cell cycle arrest and apoptosis. Notably, a high efficacy of these drugs has been selectively revealed in malignant cells rather than in normal cells. Moreover, the therapeutic potential of these agents is also supported by the evidence that HDACIs downregulate genes involved in tumor progression, invasion and angiogenesis. Several HDACIs are currently under clinical investigation, including vorinostat (SAHA), romidepsin (depsipeptide, FK-228), LAQ824/LBH589 and belinostat (PXD101), compounds that have shown therapeutic potential in many types of malignancies including solid tumors. Based on the ability of HDACIs to regulate many signaling pathways, co-treatment of these compounds with molecular targeted drugs is a promising strategy against many types of tumors.

Prospect

Regulation of histone deacetylase activities

Nilanjan Sengupta, Edward Seto *

H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612

email: Edward Seto (setoe@moffitt.usf.edu)

^*Correspondence to Edward Seto, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612.

Funded by:
National Institutes of Health; Grant Number: R01 GM58486

Keywords

HDAC • histone deacetylation • chromatin • gene regulation • protein-protein interaction • post-translational modification • subcellular localization

Abstract

Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from lysine residues in both histone and non-histone proteins. They play a key role in the regulation of gene transcription and many other biological processes involving chromatin. Significantly, recent studies suggest that HDACs are critically involved in cell-cycle regulation, cell proliferation, differentiation, and in the development of human cancer. HDAC inhibitors currently are being exploited as potential anti-cancer agents. As expected for vital regulators of many cellular processes, the activities of HDACs are tightly controlled and precisely regulated by multiple mechanisms. The activities of most if not all HDACs are regulated by protein-protein interactions. In addition, many HDACs are regulated by post-translational modifications as well as by subcellular localization. Less studied, but perhaps equally important, is the regulation of some HDACs by control of expression, availability of cofactors, and by proteolytic processing. A complete understanding of how HDACs are regulated will contribute not only to our overall knowledge of chromatin structure and gene control, but will offer tremendous insight into approaches for developing therapeutic HDAC inhibitors with improved specificity. © 2004 Wiley-Liss, Inc.