CREB-binding protein/p300 are transcriptional coactivators of p65

Abstract

CBP (CREB-binding protein) and p300 are versatile coactivators that link transcriptional activators to the basal transcriptional apparatus. In the present study, we identify CBP and p300 as coactivators of the nuclear factor-B (NF-B) component p65 (RelA). Consistent with their role as coactivators, both CBP and p300 potentiated p65-activated transcription of E-selectin and VCAM-1-CAT reporter constructs. The N-and C-terminal domains of both CBP͞p300 functionally interact with a region of p65 containing the transcriptional activation domain as demonstrated by mammalian two-hybrid assays. Direct physical interactions of CBP͞p300 with p65 were demonstrated by glutathione Stransferase fusion protein binding, and coimmunoprecipitation͞Western blot studies. The adenovirus E1A 12S protein, which complexes with CBP and p300, inhibited p65-dependent gene expression. Reporter gene expression could be rescued from E1A inhibition by overexpression of CBP or p300. CBP and p300 act as coactivators of p65-driven gene activation and may play an important role in the cytokine-induced expression of various immune and inf lammatory genes.

INK4 cell cycle inhibitors direct transcriptional inactivation of NF-κB

“…The position of proteins are indicated kBp65 and block its transactivation activity. In contrast to INK4 molecules, the basic transcription factors TFIIB and TATA-binding protein (TBP), the coactivators p300 and CBP as well as the viral encoded factor E1A 13S stimulate NF-kBp65-dependent transcription (Schmitz et al, 1996;Gerritsen et al, 1997;Paal et al, 1997;Perkins et al, 1997). These molecules directly associate with the C-terminal transactivation domain of NF-kBp65 corresponding to our observation that INK4 proteins interact with NF-kBp65, but do not interact with NF-kBp50 (Figure 2).…”

TCEAL7, a putative tumor suppressor gene, negatively regulates NF-κB pathway

“…p300 can also acetylate p65. Phosphorylation of p65 promotes the interaction with CBP, leading to enhanced transactivation potential of NF-kB (Gerritsen et al, 1997). It acts as a bridging factor between NF-kB and DNA-binding sites.…”

Expression of human p53 requires synergistic activation of transcription from the p53 promoter by AP-1, NF-κB and Myc/Max

“…Moreover, the e cient suppression of transcription by deletion of the AP-1 motif or the mutation of one of the other motifs documents a cooperativity in the transactivation from the hp53 promoter between AP-1, NF-kB, and Myc/Max. A transcriptional cooperativity that involves AP-1 and NF-kB has also been described for promoters of other genes like MHC class I (H-2K b , Brockmann et al, 1996), E-Selectin (Kaszubska et al, 1993), I-kBa (Kralova et al, 1996), IL-8 (Yasumoto et al, 1992) and IFNb (Du W et al, 1993), either involving direct (Stein et al, 1993) or indirect (Gerritsen et al, 1997) physical interaction of the respective transcription factors. Figure 3 Binding of nuclear proteins to the AP-1 motif in the human p53-promoter.…”