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Molecular and Cellular Biology, February 2000, p. 741-748, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Stimulation of p53 DNA Binding by c-Abl Requires the p53 C Terminus and Tetramerization

Ying Nie, Heng-Hong Li, Craig M. Bula, and Xuan Liu*

Department of Biochemistry, University of California, Riverside, California 92521

Received 28 June 1999/Returned for modification 29 July 1999/Accepted 21 October 1999

The carboxyl terminus of p53 is a target of a variety of signals for regulation of p53 DNA binding. Growth suppressor c-Abl interacts with p53 in response to DNA damage and overexpression of c-Abl leads to G1 growth arrest in a p53-dependent manner. Here, we show that c-Abl binds directly to the carboxyl-terminal regulatory domain of p53 and that this interaction requires tetramerization of p53. Importantly, we demonstrate that c-Abl stimulates the DNA-binding activity of wild-type p53 but not of a carboxyl-terminally truncated p53 (p53Delta 363C). A deletion mutant of c-Abl that does not bind to p53 is also incapable of activating p53 DNA binding. These data suggest that the binding to the p53 carboxyl terminus is necessary for c-Abl stimulation. To investigate the mechanism for this activation, we have also shown that c-Abl stabilizes the p53-DNA complex. These results led us to hypothesize that the interaction of c-Abl with the C terminus of p53 may stabilize the p53 tetrameric conformation, resulting in a more stable p53-DNA complex. Interestingly, the stimulation of p53 DNA-binding by c-Abl does not require its tyrosine kinase activity, indicating a kinase-independent function for c-Abl. Together, these results suggest a detailed mechanism by which c-Abl activates p53 DNA-binding via the carboxyl-terminal regulatory domain and tetramerization.

* Corresponding author. Mailing address: Department of Biochemistry, University of California, Riverside, CA 92521. Phone: (909) 787-4350. Fax: (909) 787-4434. E-mail: xuan.liu{at}ucr.edu.

Molecular and Cellular Biology, February 2000, p. 741-748, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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