Recruitment of p300/CBP in p53-Dependent Signal Pathways

Abstract

The products of the p53 and CBP/p300 genes have been individually implicated in control of cell growth and regulation of transcription. p53 is known to act as a positive and negative regulator of gene expression. Here we show that p53, in both wild-type and mutant conformation, forms a specific protein complex with p300. However, in its wild-type but not mutant conformation, p53 inhibits a promoter containing the DNA-binding sequences for the transcription factor AP1, in a p300-dependent manner. p300 stimulates the transcriptional activity of p53 on p53-regulated promoters, and it enhances the responsiveness to a physiological upstream modulator of p53 function, ionizing radiation. A dominant negative form of p300 prevents transcriptional activation by p53, and it counteracts p53-mediated G1 arrest and apoptosis. The data implicate p300 as an important component of p53-signaling, thus providing new insight into the mechanisms of cellular proliferation.

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…The human homolog is p14 ARF Regulation of p53 exerted by the C-terminal tail of p53 Modi®cations to the carboxy-terminal, including deletion of the last 30 amino-acids (Hupp et al, 1992), protein-binding (Hupp et al, 1992), phosphorylation of Ser 315 , Ser 318 and Ser 393 Wang and Prives, 1995) and recently acetylation by CREB-binding protein (CBP)/p300 (Gu and Roeder, 1997) were shown to enhance sequencespeci®c DNA-binding of wild-type p53, possibly by inhibition of p53's non-sequence-speci®c DNA-binding activity (Anderson et al, 1997). CBP and p300 are closely related histone acetyl-transferases (HATs) that interact with p53 through its amino terminus and function as coactivators for p53-mediated transcription (Avantaggiati et al, 1997;Lill et al, 1997). CBP/p300 are complexed with another HAT, p300/CBP-associated factor PCAF (Yang et al, 1996).…”

Additive effect between NF-κB subunits and p53 protein for transcriptional activation of human p53 promoter

“…HCT116 cells were cotransfected with p53 WT-LUC (0.5 mg), p53 MT1-LUC (0.5 mg) or p53 MT2-LUC (0.5 mg) reporter plasmids together with RSV-bGAL (0.4 mg). Transfected cells were treated with 1 or 2 mM daunomycin for 6 h. LUC and bGAL activities were determined as described in Figure 2 (HIF1a) (Avantaggiati et al, 1997;Blagosklonny et al, 1998). The p53/Sp1 complex displays, in vitro, a high a nity for Sp1 or p53 consensus sites and positively regulates target gene expression (Borellini and Glazer, 1993;Gualberto and Baldwin, 1995), while the association between p53 and WT1 increases p53 stability, its transcriptional activity and gadd45 expression (Zhan et al, 1998).…”

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

“…Binding of p300/CBP by E1A inhibits the transcription of the p21 CIP1/WAF1 induced by DNA damage (Steegenga et al, 1996;Somasundaram and el-Deiry, 1997), transforming growth factor-b (TGF-b) (Datto et al, 1997), keratinocytes and myoblasts terminal differentiation (Missero et al, 1995;Cenciarelli et al, 1999). In the cases above mentioned, the transcription of p21 CIP1/WAF1 depends either on p53 (Vogelstein et al, 2000) or on differentiation-specific factors like MyoD (Cenciarelli et al, 1999), RB family proteins and small DNA virus oncoproteins A Felsani et al and p300/CBP is the transcriptional coactivator both of p53 (Avantaggiati et al, 1997;Lill et al, 1997) and MyoD (Eckner et al, 1996;Yuan et al, 1996). The interaction of E1A N-terminal region with p400, a member of SWI2/SNF2 chromatin remodeling complex (Fuchs et al, 2001), may also deregulate the p53-p21 CIP1/WAF1 pathway, leading to a downregulation of p21 CIP1/WAF1 (Chan et al, 2005).…”