Characterization of a p53 Regulatory Domain

Abstract

We purposed to characterize a regulatory domain on p53 and identify kinase(s) that may be involved in the regulation. Since 7/1/97, we constructed a set of deletions to disrupt the potential regulatory domains of p53 on Gal4-p53(1-160) and on full-length p53. Using these mutants we have obtained the following results: 1. Mutants Gal4-p53N(Delta92- 109), Gal4-p53N (Al17-128) and Gal4-p53N (Ser117/l27Ala) had little effect on the putative inhibitory effect. 2. TPA stimulation inhibited the transcriptional activities of Gal4-p53N (DELTA92-109) and (Ga14-p53N (Delta117-128), but did not affect Gal4-p53(1-92). 3. Mutants p53(DELTA92-109), p53(Deltas117-128), p53(Sl17/127A) and p53(S117/127D) significantly lost their ability to activate transcription in vivo. 4. Mutants p53(DELTA92-109), p53(DELTA117-128) and p53(S117/127A) retained their abilities to bind to DNA, but p53(S1 17/127D) not. 5. MAP-kinase is involved in the degradation of mutant p53 protein. In conclusion, we have shown that two serine residues 117 and 127 may play a role in stabilization of p53 protein levels. Further experiments will be conducted to confirm these results. We have also showed that MAP-kinase is involved in the degradation of mutant p53 protein. Our findings suggest a role for MAPK in the degradation of mutated form of p53 protein and in cell differentiation. These% results were published as a JBC paper

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2000
Accession Number
ADA387794

Entities

People

  • Brian C. Abela
  • Xuan Liu

Organizations

  • University of California, Riverside

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DTIC Thesaurus Topics

  • Albumins
  • Biochemistry
  • Biomedical And Dental Materials
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Detection
  • Materials
  • Molecular Biology
  • Neoplasms
  • Polymer Chemistry
  • Polymeric Films
  • Proteins
  • Recombinant Dna
  • Transcription Factors

Fields of Study

  • Biology

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  • Analytical Mechanics
  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Genetics