Accession Number:

ADA361656

Title:

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

Descriptive Note:

Annual rept. 1 Jun 97-31 May 98

Corporate Author:

CALIFORNIA UNIV RIVERSIDE

Personal Author(s):

Report Date:

1998-06-01

Pagination or Media Count:

12.0

Abstract:

Since this grant was awarded 7196, we have constructed a set of deletion mutants and showed 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 proposed a model in which c-Abl interacts with the regulatory domain aa 363 to 393 on p53 to diminish its negative regulatory effect and thereby to enhance the DNA binding activity of p53. This interaction, however, requires the tetrameric conformation of the protein To test this, we first investigated the ability of a mutant p53 341K344E348E355K, tetramerization impair to interact with c-Abl and showed that this mutant is defective in c-Abl interaction. Second, we proposed to obtain the purified c-Abl protein via a baculovirus expression system to assay its ability to enhance p53,s DNA binding. Unfortunately, we have not been able to do so using c-Abl virus we have. We are currently in a process to construct a new virus which expresses His-tag c-Abl. We hope that we will be able to obtain a large amount of purified protein to enable us to perform EMSA experiments as we proposed.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE