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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 must be competent for transcriptional regulation to suppress tumor formation

Monica Nistér1, Mengjia Tang, Xiao-Qun Zhang

  • 1Department of Oncology-Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Oncogene
|March 8, 2005
PubMed

Insights

The tumor suppressor protein p53

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • p53 protein's tumor suppression involves both transcription-dependent and -independent functions.
  • The role of p53's transactivation domain in tumor suppression in vivo is not fully understood.

Purpose of the Study:

  • To investigate the necessity of p53's transactivation function for tumor suppression.
  • To determine if p53 possesses significant in vivo tumor suppressor functions independent of transcriptional regulation.

Main Methods:

  • Generation of a mutant p53 allele (p53(W25QL26S)) in mice with an inactive transactivation domain.
  • Characterization of the mutant p53 allele's DNA binding, chromatin association, and transcriptional activity.
  • Assessment of tumor suppression in mice carrying the mutant p53 allele in spontaneous and oncogene-induced tumorigenesis models.

Main Results:

  • The mutant p53 allele (p53(QSval135)) exhibited impaired transcriptional regulation and apoptosis induction.
  • Mice with the p53(QSval135) allele showed tumor development kinetics and spectra identical to p53-null mice.
  • The p53(QSval135) allele did not display dominant-negative effects and functioned as a null allele.

Conclusions:

  • Effective tumor suppression by p53 in vivo critically relies on its transcriptional regulation function.
  • Transactivation-independent functions of p53 are unlikely to play a significant role in in vivo tumor suppression.

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