Fig. 2

Defects in p300/CBP activation or repression of transcription that result in tumorigenesis. (A) CBP interaction domains. The KIX (kinase-inducible interaction) domain mediates interactions with phosphorylated CREB and STAT1α. C/H3 is a cysteine-histidine-rich region that mediates interactions with several factors, including E1A, STAT1α and complex of RNA helicase A and RNA polymerase II. The region in CBP that interacts with nuclear receptor coactivators is indicated as NCoA. Numbers above CBP indicate endpoints of CBP deletion mutants. [Redrawn from Kurokawa et al., 199836.] (B) CBP misfunction and cancer. The transcriptional coactivator CBP responds to numerous signals in regulating normal cell growth and development. Abrogation of CBP functions is linked to at least three oncogenic events. CBP normally associates with the histone acetyltransferase P/CAF. Displacement of P/CAF occurs upon E1A and SV40 T antigen binding to CBP and this displacement contributes to cellular transformation. Fusion of CBP to translocated MOZ sequences is associated with specific subtypes of acute myeloid leukemias, and mutation of CBP leads to development of Rubinstein-Taybi syndrome. Substitution or loss of acetyltransferase activities (*) are now known to be involved in two of these three instances of CBP-related oncogenesis. [Adapted with permission from Roth, 199637.]