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CBP/p300 and lung cancer 324
Cell Research (2007) 17: 324-332 2007 IBCB, SIBS, CAS All rights reserved 1001-0602/07 $ 30.00
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REVIEW
www.nature.com/cr
Roles of CREB-binding protein (CBP)/p300 in respiratory epithelium tumorigenesis
Michalis V Karamouzis1, Panagiotis A Konstantinopoulos1, 2, Athanasios G Papavassiliou1
1Department of Biological Chemistry, Medical School, University of Athens, 75, M Asias Street, 11527 Athens, Greece; 2Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
CREB-binding protein (CBP) and its homologue p300 are transcriptional co-activators of various sequence-specic transcription factors that are involved in a wide array of cellular activities, such as DNA repair, cell growth, differentiation and apoptosis. Several studies have suggested that CBP and p300 might be considered as tumour suppressors, with their prominent role being the cross-coupling of distinct gene expression patterns in response to various stimuli. They exert their actions mainly via acetylation of histones and other regulatory proteins (e.g. p53). A major paradox in CBP/ p300 function is that they seem capable of contributing to various opposed cellular processes. Respiratory epithelium tumorigenesis represents a complex process of multi-step accumulations of a gamut of genetic and epigenetic aberrations. Transcription modulation through the alternate formation of activating and repressive complexes is the ultimate converging point of these derangements, and CBP/p300 represents key participants in this interplay. Thus, illumination of their molecular actions and interactions could reveal new potential targets for pharmacological interventions in respiratory epithelium carcinogenesis.
Keywords: CBP, p300, lung cancer, acetylation, transcription factor
Cell Research (2007) 17:324-332. doi: 10.1038/cr.2007.10; published online 20 March 2007
Introduction
cAMP response element-binding protein-binding protein (CBP) and p300 were originally identied as factors binding to the cAMP response element-binding protein (CREB) and the adenoviral E1A, respectively [1, 2]. The human CBP locus resides in the chromosomal region 16p13.3 and shows homology to 22q13, where p300 is located [3]. CBP/p300 proteins share several conserved regions, which constitute most of their known functional domains (Figure 1). CBP and p300 have interchangeable roles during embryonic development and in many processes govern cellular homeostasis [4, 5]. However, genetic and molecular evidence suggests that they also full distinct functions [3]. Homozygous CBP/ and p300/ knockout mice were inviable due to severe developmental de-
fects, albeit abnormal heart formation was noted only...