CNOT2 promotes degradation of p62/SQSTM1 as a negative regulator in ATG5 dependent autophagy

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Kwon Jeong1, Hee Young Kwon1, Myoung Seok Jeong1

  • 1Cancer Molecular Targeted Herbal Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Republic of Korea.

Oncotarget
|May 25, 2017
PubMed

Insights

CNOT2 negatively regulates autophagy by targeting p62/SQSTM1 for degradation. This study reveals CNOT2

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • CNOT2 is known to regulate adipogenesis, apoptosis, and metastasis.
  • The specific role of CNOT2 in autophagy remained unclear prior to this study.

Purpose of the Study:

  • To elucidate the role of CNOT2 in autophagy.
  • To investigate the association between CNOT2 and p62/SQSTM1 signaling in autophagy.

Main Methods:

  • Investigated CNOT2's effect on p62/SQSTM1 and LC3B-II levels.
  • Utilized cell lines including HEK293 QBI, H1299, and MEF cells.
  • Employed autophagy inhibitors and analyzed protein ubiquitination and degradation.

Main Results:

  • CNOT2 depletion caused p62/SQSTM1 accumulation and impaired autophagic flux.
  • CNOT2 overexpression led to p62/SQSTM1 downregulation and ubiquitination.
  • CNOT2-mediated p62/SQSTM1 degradation was dependent on ATG5.

Conclusions:

  • CNOT2 acts as a negative regulator of autophagy.
  • The findings highlight CNOT2's critical role in ATG5-dependent autophagy via p62/SQSTM1 signaling.
Keywords:
ATG5CNOT2PB1 domainautophagyp62/SQSTM1

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