Chromatin remodeling, cancer and chemotherapy.
DNA in eukaryotic nucleus is highly condensed with histone proteins as nucleosomes. Three dimensional arrangements of nucleosomes give rise to the formation of chromatin. Extensive studies in the recent years have highlighted that the structure of chromatin plays a critical role in gene expression. Post translational modifications (such as acetylation, deacetylation, methylation and phosphorylation etc.) of tails of histones may occur with the help of various histone modifier proteins which may lead to architectural changes of nucleosomes and chromatin remodeling. Chromatin remodeling may finally enhance or repress gene transcriptions. The neoplastic cells selectively take the advantages of histone modifications for the cell proliferation, differentiation and evasion of apoptosis. There are enough experimental and clinical evidences that various histone modifiers are linked with many human malignancies. The thorough knowledge of manipulation of histone modifiers by cancer cells may help us to design newer anti-neoplastic drugs in future. There is considerable interest in histone deactylase inhibitors as antineoplastic agents and various clinical trials are in progress. This article reviews a general overview of chromatin remodeling proteins, their role in carcinogenesis and the future potential of the histone deacetylase inhibitors in cancer chemotherapy.
Dey
Pranab
P
Department of Cytology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. deypranab@hotmail.com
D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D009707:Nucleosomes / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation
D000970:Antineoplastic Agents; D002843:Chromatin; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009707:Nucleosomes