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Cited by 180

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

Histone Acetylation Modifiers in the Pathogenesis of Malignant Disease

Open access
Mahlknecht, Ulrich, Hoelzer, Dieter·2000·Molecular Medicine
DOI 10.1007/bf03402044
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Abstract

Chromatin structure is gaining increasing attention as a potential target in the treatment of cancer. Relaxation of the chromatin fiber facilitates transcription and is regulated by two competing enzymatic activities, histone acetyltransferases (HATs) and histone deacetylases (HDACs), which modify the acetylation state of histone proteins and other promoter-bound transcription factors. While HATs, which are frequently part of multisubunit coactivator complexes, lead to the relaxation of chromatin structure and transcriptional activation, HDACs tend to associate with multisubunit core-pressor complexes, which result in chromatin condensation and transcriptional repression of specific target genes. HATs and HDACs are known to be involved both in the pathogenesis as well as in the suppression of cancer. Some of the genes encoding these enzymes have been shown to be rearranged in the context of chromosomal translocations in human acute leukemias and solid tumors, where fusions of regulatory and coding regions of a variety of transcription factor genes result in completely new gene products that may interfere with regulatory cascades controlling cell growth and differentiation. On the other hand, some histone acetylation-modifying enzymes have been located within chromosomal regions that are particularly prone to chromosomal breaks. In these cases gains and losses of chromosomal material may affect the availability of functionally active HATs and HDACs, which in turn disturbs the tightly controlled equilibrium of histone acetylation. We review herein the recent achievements, which further help to elucidate the biological role of histone acetylation modifying enzymes and their potential impact on our current understanding of the molecular changes involved in the development of solid tumors and leukemias.

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Metadata

Authors
Mahlknecht, U., & Hoelzer, D.
Venue
Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2000-08
Volume
6
Issue
8
Pages
623-644
ISSN
  • 1076-1551 (ISSN-L)
  • 1528-3658
DOI
10.1007/bf03402044
OpenAlex
W1574682683
Cited by
180
References
21
FWCI
2.03
Type
journal article
Language
en
Open access
gold

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