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Updated: Jan 30, 2026

Detection of Protein Ubiquitination
Published on: August 19, 2009
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.
Abstract:
The evolutionarily conserved mTOR signaling pathway plays essential roles in cell growth, proliferation, metabolism and responses to cellular stresses. Hyperactivation of the mTOR signaling is observed in virtually all solid tumors and has been an attractive drug target. In addition to changes at genetic levels, aberrant activation of the mTOR signaling is also a result from dysregulated posttranslational modifications on key pathway members, such as phosphorylation that has been extensively studied. Emerging evidence also supports a critical role for ubiquitin-mediated modifications in dynamically regulating the mTOR signaling pathway, while a comprehensive review for relevant studies is missing. In this review, we will summarize characterized ubiquitination events on major mTOR signaling components, their modifying E3 ubiquitin ligases, deubiquitinases and corresponding pathophysiological functions. We will also reveal methodologies that have been used to identify E3 ligases or DUBs to facilitate the search for yet-to-be discovered ubiquitin-mediated regulatory mechanisms in mTOR signaling. We hope that our review and perspectives provide rationales and strategies to target ubiquitination for inhibiting mTOR signaling to treat human diseases.
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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