Journal
GENES & DEVELOPMENT
Volume 20, Issue 18, Pages 2566-2579Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1455006
Keywords
AKAP; aurora; HDAC; histone code; mitosis
Categories
Funding
- NCI NIH HHS [CA-107956, R01 CA107956] Funding Source: Medline
- NIDDK NIH HHS [P30 DK019525, DK19525, DK062434, U19 DK062434] Funding Source: Medline
- NIGMS NIH HHS [R01 GM037537, GM37537] Funding Source: Medline
Ask authors/readers for more resources
Histone deacetylase (HDAC) inhibitors perturb the cell cycle and have great potential as anti-cancer agents, but their mechanism of action is not well established. HDACs classically function as repressors of gene expression, tethered to sequence-specific transcription factors. Here we report that HDAC3 is a critical, transcription-independent regulator of mitosis. HDAC3 forms a complex with A-Kinase-Anchoring Proteins AKAP95 and HA95, which are targeted to mitotic chromosomes. Deacetylation of H3 in mitosis requires AKAP95/HA95 and HDAC3 and provides a hypoacetylated H3 tail that is the preferred substrate for Aurora B kinase. Phosphorylation of H3S10 by Aurora B leads to dissociation of HP1 proteins from methylated H3K9 residues on mitotic heterochromatin. This transcription-independent pathway, involving interdependent changes in histone modification and protein association, is required for normal progression through mitosis and is an unexpected target of HDAC inhibitors, a class of drugs currently in clinical trials for treating cancer.
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