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CUL5-ASB6 Complex Promotes p62/SQSTM1 Ubiquitination and Degradation to Regulate Cell Proliferation and Autophagy

Liyan Gong1,2, Kaihua Wang3,4, Mengcheng Wang3,4

  • 1Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.

Frontiers in Cell and Developmental Biology
|June 24, 2021
PubMed

Insights

The CUL5-ASB6 complex targets p62/SQSTM1 for degradation, impacting cell proliferation and autophagy. This discovery offers new insights into p62 regulation in diseases like cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • p62/SQSTM1 (sequestosome-1) is crucial for cellular processes like autophagy, nutrient sensing, and cell survival.
  • Dysregulation of p62 is linked to human diseases, including obesity and cancer.

Purpose of the Study:

  • To identify the molecular mechanism regulating p62/SQSTM1 ubiquitination and degradation.
  • To investigate the role of the CUL5-ASB6 complex in p62 stability and its functional consequences.

Main Methods:

  • Investigated the interaction between CUL5-ASB6 complex and p62/SQSTM1.
  • Utilized gene depletion and overexpression techniques to study p62 levels.
  • Assessed the impact of ASB6 on cell proliferation and autophagy.

Main Results:

  • The CUL5-ASB6 complex was identified as a ubiquitin E3 ligase that mediates p62 ubiquitination and degradation.
  • Depletion of CUL5 or ASB6 led to p62 accumulation.
  • Overexpression of ASB6 resulted in decreased p62 levels, inhibited proliferation of MEF and hepatocellular carcinoma cells, and impaired autophagy.

Conclusions:

  • The study elucidates a novel mechanism for p62/SQSTM1 regulation via the CUL5-ASB6 ubiquitin E3 ligase complex.
  • This finding provides insights into the control of p62 stability, cell proliferation, and autophagy in health and disease.
Keywords:
ASB6CUL5autophagyp62proliferationubiquitination

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