Stimulation of p53-Dependent Transcription by the Growth Suppressor, c- Abl

摘要

Although it is known that c-Abl stimulates p53-dependent transcription, a function required for c-Abl growth suppressor activity, the molecular mechanism by which this occurs remain elusive. The results obtained with this grant award show that c-Abl interacts with the C-terminal regulatory domain of tetrameric form of p53 and functions to activate the p53 DNA-binding. In an effort to assess the mechanism of c-Abl activation, we also show that c- Abl activates p53 DNA-binding by stabilizing the p33-DNA complex. Collectively, these results suggest a model for c-Abl activation. In this model c-Abl activates latent p53 by relieving the C-terminal inhibitory domain of p53 and enhances p53 DNA-binding by forming a stable p53-DNA complex (see text).