Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 378, Issue 3, Pages 326-331Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.11.057
Keywords
Histone deacetylase; Trichostatin A; Transcription; Cell cycle; Cell death
Categories
Funding
- Korea Health Development Institute [A08-0542-AA1723-08N1-00010A]
- National Research Foundation of Korea [과C6A2602] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Histone deacetylases (HDACs), a promising target for cancer therapy, play a role in regulating cell-cycle progression. The mechanisms for HDAC inhibition-induced regulation of G(2)/M transition and mitotic progression remain to be elucidated. Herein, we report that trichostatin A (TSA), an HDAC inhibitor, induces a delay at the G(2)/M transition, chromosome missegregation and multi-nucleation. and thereby leads to cell death by promoting exit from aberrant mitosis without spindle checkpoint. These results are associated with a transcriptional modulation of key regulator genes of the cell cycle, including CyclinB1, PIk1, Survivin, and P21(WAF1/Cip1). Actinomycin D, a transcriptional inhibitor, abrogated the TSA-induced delay of G(2)/M transition and transcriptional modulation of cell-cycle regulator genes, indicating that the impact of TSA in this manner is transcription dependent. Overall, our findings indicate that TSA provides a barrier to cell-cycle progression for antiproliferation and promotes escape from mitotic catastrophe and cell death, by inhibiting an HDAC-mediated transcriptional action. (C) 2008 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available