CBP as β-Catenin Partner

Science's STKE  14 Nov 2000:
Vol. 2000, Issue 58, pp. tw5
DOI: 10.1126/stke.2000.58.tw5

The transcriptional coactivator proteins CBP and p300 have histone acetyltransferase activity and are implicated in control of cell proliferation and differentiation. Miyagishi et al. now provide evidence that CBP/p300 interacts with β-catenin (the scaffold protein of the Wnt signaling pathway that acts to promote transcription through interactions with the TCF and Lef transcription factors). In human colon carcinoma HCT116 cells (in which β-catenin is mutated and stabilized), endogenous CBP/p300 was associated with β-catenin. The β-catenin interacted with the same region of CBP known to interact with a number of other nuclear target proteins that influence proliferation and apoptosis. In cotransfection experiments in mouse L cells, CBP/p300 enhanced transcription of a reporter gene activated by β-catenin. In HeLa cells, transfection with a stable β-catenin mutant inhibited apoptosis dependent on the tumor supressor protein p53. The authors propose that if amounts of CBP/p300 are limiting, competitive inhibition by β-catenin could influence activity of p53 and other CBP/p300 targets.

Miyagishi, M., Fujii, R., Hatta, M., Yoshida, E., Araya, N., Nagafuchi, A., Ishihara, S., Nakajima, T., and Fukamizu, A. (2000) Regulation of Lef-mediated transcription and p53-dependent pathway by associating β-catenin with CBP/p300. J. Biol. Chem. 275: 35170-35175. [Full Text] [Abstract]