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Zhu, P.* ; Huber, E. ; Kiefer, F. ; Göttlicher, M.

Specific and redundant functions of histone deacetylases in regulation of cell cycle and apoptosis.

Cell Cycle 3, 115-117 (2004)

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Inappropriate control of expression of genetic information is the cause of many forms ofcancer. Aberrant transcriptional repression by recruitment of histone deacetylases (HDACs) isa key step in pathogenesis of myeloid leukemia. We recently reported that development ofcolonic cancer involves alterations in the transcriptional repression machinery by increasedexpression of HDAC 2 upon loss of the APC tumor suppressor. Increased expression ofHDAC 2 is essential for prevention of apoptosis of HT-29 colonic cancer cells. We nowdiscuss whether HDAC 2 also plays a role for aberrant cell cycle regulation and expression ofthe p21Cip/Waf cell cycle inhibitor. Whereas inhibition of HDACs by valproic acid ortrichostatin A increases p21 expression, selective interference with HDAC 2 by siRNAtransfection or reconstitution of wildtype APC does not affect p21 expression. Likewise,treatment of HT-29 cells with the HDAC inhibitor valproic acid leads to a moderate inhibitionof cell cycle progression in the G1 phase whereas interference with HDAC2 expression doesnot. Thus, HDAC 2 appears to serve a preferential role in the prevention of apoptosis and notin cell cycle control similar to the specific importance of HDAC 1 for cell cycle regulation orHDAC 9 for the stress response of the heart.

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