Control of mTOR signaling by ubiquitin

Yao Jiang1,2, Siyuan Su2, Yanqiong Zhang2

  • 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.

Oncogene
|February 2, 2019
PubMed

Insights

Ubiquitin modification dynamically regulates the mTOR pathway, crucial in cell growth and cancer. This review details ubiquitination on mTOR components, E3 ligases, and deubiquitinases, offering strategies to target this for disease treatment.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Oncology

Background:

  • The mechanistic target of rapamycin (mTOR) signaling pathway is vital for cell growth, proliferation, metabolism, and stress responses.
  • Hyperactivation of mTOR signaling is a hallmark of most solid tumors, making it a key therapeutic target.
  • While genetic alterations and phosphorylation are well-studied, the role of ubiquitin-mediated modifications in mTOR regulation is increasingly recognized but not comprehensively reviewed.

Purpose of the Study:

  • To provide a comprehensive review of characterized ubiquitination events on major mTOR signaling components.
  • To identify the E3 ubiquitin ligases and deubiquitinases (DUBs) involved in mTOR pathway regulation.
  • To discuss the pathophysiological functions of these ubiquitination events and propose strategies for therapeutic targeting.

Main Methods:

  • Literature review of studies characterizing ubiquitination on mTOR pathway members.
  • Analysis of identified E3 ligases and DUBs affecting mTOR signaling.
  • Discussion of methodologies used for identifying E3 ligases and DUBs in this pathway.

Main Results:

  • Summarizes known ubiquitination events on key mTOR pathway proteins.
  • Details the specific E3 ligases and DUBs responsible for these modifications.
  • Highlights the impact of these modifications on cellular processes and disease, particularly cancer.

Conclusions:

  • Ubiquitination is a critical, dynamic regulatory mechanism for the mTOR signaling pathway.
  • Targeting E3 ligases and DUBs involved in mTOR ubiquitination offers novel therapeutic strategies for human diseases, especially cancer.
  • Further research into undiscovered ubiquitination events can uncover new avenues for mTOR-targeted therapies.

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