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UBE2B promotes ovarian cancer growth via promoting RAD18 mediated ZMYM2 monoubiquitination and stabilization

Xi Zeng1, Wen Zheng2, Yuting Sheng1

  • 1Department of Obstetrics & Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Bioengineered
|March 22, 2022
PubMed

Insights

The UBE2B/RAD18 complex regulates ZMYM2 stability and monoubiquitination in ovarian cancer. This interaction promotes tumor growth, offering potential therapeutic targets for ovarian cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Ubiquitin-conjugating enzyme E2 B (UBE2B) forms a complex with ubiquitin E3 ligase RAD18.
  • The regulatory roles of the UBE2B/RAD18 complex in ovarian cancer are not fully understood.
  • Identifying novel substrates and their functions is crucial for understanding cancer progression.

Purpose of the Study:

  • To investigate new substrates of the UBE2B/RAD18 complex in ovarian cancer.
  • To elucidate the regulatory effects of the UBE2B/RAD18 complex on ZMYM2.
  • To assess the impact of the UBE2B-ZMYM2 axis on ovarian cancer growth in vivo.

Main Methods:

  • Protein interaction prediction (GeneMANIA), immunohistochemistry on ovarian cancer tissue arrays.
  • Immunofluorescence staining, co-immunoprecipitation, and cycloheximide chase assays.
  • Xenograft tumor models in mice.

Main Results:

  • A positive correlation was observed between UBE2B, RAD18, and ZMYM2 expression in ovarian cancer tissues.
  • UBE2B/RAD18 complex directly interacts with ZMYM2, promoting its monoubiquitination and protein stability.
  • UBE2B overexpression enhances ovarian tumor growth, while ZMYM2 knockdown suppresses it.

Conclusions:

  • The UBE2B/RAD18 complex plays a critical role in regulating ZMYM2 monoubiquitination and stability.
  • The UBE2B-ZMYM2 axis promotes ovarian cancer progression.
  • Targeting the UBE2B/RAD18-ZMYM2 pathway may offer a novel therapeutic strategy for ovarian cancer.
Keywords:
RAD18UBE2BZMYM2monoubiquitinationovarian cancer

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