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The RNA binding protein RALY suppresses p53 activity and promotes lung tumorigenesis

Hao Hu1, Kailiang Zhao1, Debao Fang1

  • 1Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, Anhui, China.

Cell Reports
|March 23, 2023
PubMed

Insights

The RNA binding protein RALY promotes lung cancer by stabilizing Mdm2 and enhancing the degradation of the tumor suppressor p53. RALY acts as an oncogenic factor by inhibiting p53 activity.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The tumor suppressor p53 is crucial for preventing cancer.
  • Mdm2, an E3 ligase, restrains p53 activity, but its regulation is complex.
  • Understanding the Mdm2-p53 pathway is vital for cancer research.

Purpose of the Study:

  • To investigate the role of RNA binding protein RALY in lung cancer.
  • To elucidate the mechanism by which RALY influences the Mdm2-p53 pathway.
  • To determine if RALY functions as an oncogenic factor in lung tumorigenesis.

Main Methods:

  • Investigated RALY's interaction with Mdm2 and USP7.
  • Assessed RALY's effect on Mdm2 stability and Mdm2's E3 ligase activity.
  • Evaluated RALY's impact on p53 ubiquitination and degradation.
  • Examined RALY's role in lung tumorigenesis in vivo.

Main Results:

  • RALY binds to both Mdm2 and USP7, stabilizing Mdm2.
  • RALY enhances Mdm2's E3 ligase activity towards p53.
  • RALY promotes p53 ubiquitination and degradation, inhibiting its tumor-suppressive function.
  • RALY promotes lung tumorigenesis, partly through p53 inhibition.

Conclusions:

  • RALY acts as an oncogenic factor in lung cancer by destabilizing p53.
  • RALY modulates Mdm2 function at multiple levels to inhibit p53.
  • RALY represents a potential therapeutic target for lung cancer treatment.
Keywords:
CP: CancerCP: Molecular biologyMdm2RALYUSP7p53tumorigenesis

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