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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

Yin Yang 1 is a negative regulator of p53

Guangchao Sui1, El Bachir Affar, Yujiang Shi

  • 1Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

Cell
|June 24, 2004
PubMed

Insights

Yin Yang 1 (YY1) acts as a cofactor for Hdm2, promoting p53 protein degradation. This discovery clarifies YY1

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Yin Yang 1 (YY1) is a crucial transcription factor in development.
  • The complete functions and mechanisms of YY1 are not fully understood.

Purpose of the Study:

  • To investigate the role of YY1 in regulating p53 stability.
  • To elucidate the mechanism by which YY1 affects p53 levels.

Main Methods:

  • YY1 ablation and overexpression in vivo.
  • In vitro studies with recombinant YY1.
  • Co-immunoprecipitation assays to detect protein interactions.
  • Analysis of p53 ubiquitination and degradation.

Main Results:

  • YY1 deficiency leads to p53 accumulation by reducing its ubiquitination.
  • YY1 overexpression enhances p53 ubiquitination and degradation.
  • YY1 directly interacts with Hdm2 and p53, facilitating Hdm2-p53 binding.
  • p14ARF disrupts the Hdm2-YY1 interaction, impacting YY1's regulation of p53.

Conclusions:

  • YY1 functions as a cofactor for Hdm2 in regulating p53 homeostasis.
  • YY1's role in p53 regulation is independent of its transcriptional activity.
  • YY1 may play a role in tumorigenesis through p53 pathway modulation.

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