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

Published on: August 4, 2019

p73 expression is regulated by RNPC1, a target of the p53 family, via mRNA stability

Wensheng Yan1, Jin Zhang, Yanhong Zhang

  • 1Comparative Oncology Laboratory, University of California at Davis, Davis, California, USA.

Molecular and Cellular Biology
|April 18, 2012
PubMed

Insights

The RNA binding protein RNPC1 regulates p73 mRNA stability, impacting tumor suppression and neural development. This RNPC1-p73 feedback loop offers a potential therapeutic target for p53-deficient tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • p73, a p53 family tumor suppressor, plays critical roles in tumor suppression and neural development.
  • p73 expression and activity are tightly regulated through various mechanisms, including transcription and posttranslational modifications.

Purpose of the Study:

  • To investigate the role of RNA-binding protein 1 (RNPC1) in regulating p73 mRNA stability.
  • To elucidate the physiological significance of RNPC1-mediated regulation of p73 expression in cellular processes like proliferation and senescence.
  • To explore the potential of the RNPC1-p73 regulatory axis as a therapeutic target in p53-deficient cancers.

Main Methods:

  • Analysis of p73 mRNA stability regulation by RNPC1.
  • Identification of a CU-rich element in the 3' untranslated region of p73 recognized by RNPC1.
  • Assessment of RNPC1's impact on p73, p21, p130, and γ-H2A.X expression in p53-null mouse embryonic fibroblasts.
  • Evaluation of the effects of TAp73 and p21 knockdown on RNPC1's influence on cell proliferation and senescence.

Main Results:

  • RNPC1 directly regulates p73 mRNA stability by recognizing a CU-rich element in its 3' untranslated region.
  • Loss of RNPC1 in p53-null cells leads to reduced p73, p21, p130, and γ-H2A.X expression, and decreased cellular senescence.
  • RNPC1 inhibits cell proliferation and induces premature senescence, effects that are attenuated by TAp73 or p21 knockdown and abolished by combined knockdown.
  • A novel feed-forward loop exists between p73 and RNPC1, as RNPC1 is a target of p73.

Conclusions:

  • RNPC1 is a key regulator of p73 mRNA stability, influencing critical cellular processes.
  • The mutual regulation between p73 and RNPC1 forms a feed-forward loop with implications for p53-deficient tumors.
  • Targeting the RNPC1-p73 pathway presents a promising therapeutic strategy for cancers lacking functional p53.

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