Visit our Expo - Redox and Inflammation signaling 2012

Session XIII : Cell signaling pathways leading to regulated chromatin modifications
Poster XIII, 11
The role of p300/CBP complex in the differential regulation of apoptosis induced by
diverse types of cytotoxic stress
G. Xenaki1, M. Krstic-Demonacos2, C. Demonacos1
University of Manchester 1. School of Pharmacy, Coupland 3 building, and
2. Faculty of Life Sciences, Michael Smith building, Oxford Road, Manchester, M13
9PL
The underlying mechanisms triggering apoptosis have been unravelled in recent years and it
is accepted that diverse apoptotic stimuli (anti-cancer drugs, $- or UV-irradiation, cytokines,
hypoxia, deprivation of survival factors) converge on a common cascade of events leading to
apoptosis. The Bcl-2 family members play a central role in these apoptotic events. Protein
complexes that include transcription factors and coactivators (p300, P/CAF HATs) or
repressors (HDACs) frequently govern the expression of this specific set of genes in order to
delicately balance the protein levels of anti- and pro-apoptotic members of this family and
eventually determine the cell fate. The main focus of our work is to dissect the regulatory
pathways determining the cellular fate under diverse stress conditions. We have observed that
differential composition of the transcription co-activator complexes under diverse stress
conditions fine tune the protein levels of pro- and anti apoptotic members of the Bcl-2 family
determining whether the cell will survive or die through apoptosis
. In particular, we have studied the expression of Bid, a pro-apoptotic member of the Bcl-2
family, under conditions known to activate the p53 and/or Hif-1" transcription factors
(binding sites for both transcription factors have been identified in the Bid promoter region).
We have identified this way the cellular components regulating the mRNA synthesis of Bid
under diverse stress conditions. In this context our studies have provided evidence that two
components of the p300/CBP complex namely Strap and P/CAF directly or indirectly mediate
critical signalling events that regulate both p53 and Hif-1" transcriptional activities under
hypoxia.
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