Accession Number : ADA332767

Title :   Stimulation of p53-dependent Transcription by the Growth Suppressor, c-Abl.

Descriptive Note : Annual rept. 1 Jun 96-31 May 97

Corporate Author : CALIFORNIA UNIV RIVERSIDE

Personal Author(s) : Liu, Xuan ; Cogan, John

PDF Url : ADA332767

Report Date : JUL 1997

Pagination or Media Count : 13

Abstract : Since this grant was awarded (7/1/96), we have constructed a set of deletions to disrupt the domains of p53 responsible for nuclear localization (aa 316 to 322), tetramerization (aa 325 to 356) and the regulation of the DNA binding activity of p53 (aa 363 to 393). Furthermore, the ability of these mutants to interact with c-Abl was also tested using a GST pull-down assay. Our results show that deletion of last 30 amino acids in p53 severely disrupted its ability to bind to c-Abl and deletion of the tetramerization domain also greatly reduced the binding to c-Abl. Based on these results, we propose a model in which c-Abl interacts with the regulatory domain (aa 363 to 393) in p53 to diminish its negative regulatory effect and to enhance the DNA binding activity of p53. This interaction, however, requires the tetrameric conformation of the protein. To test this requirement, ability of a mutant p53 (341K344E348E355K, tetramerization impair) to interact with c-Abl was investigated. Our results show this mutant is defective in c-Abl interaction. We are currently examining the effect of c-Abl on DNA binding activity of p53.

Descriptors :   *CELLS(BIOLOGY), *SUPPRESSORS, *BREAST CANCER, STIMULATION(PHYSIOLOGY), PROTEINS, DEOXYRIBONUCLEIC ACIDS, MUTATIONS, IN VIVO ANALYSIS, GROWTH(PHYSIOLOGY).

Subject Categories : Biochemistry
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE