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Yin Yang 1 promotes mTORC2-mediated AKT phosphorylation
Qiang Zhang1, Meimei Wan2, Jinming Shi3
1College of Life Science, Northeast Forestry University, Harbin, China Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA Present address: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Journal of Molecular Cell Biology
|January 15, 2016
Summary
Yin Yang 1 (YY1) drives cancer cell proliferation by activating AKT. A peptide targeting the YY1-AKT interaction inhibits this activation, offering a potential new cancer therapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Yin Yang 1 (YY1) is a transcription factor involved in gene regulation and protein modification.
- YY1 has a known role in promoting cancer cell proliferation.
- AKT phosphorylation at S473 is a key marker for AKT pathway activation.
Purpose of the Study:
- To investigate the role of YY1 in AKT activation and its implications in breast cancer.
- To identify the mechanism by which YY1 promotes AKT phosphorylation.
- To explore the therapeutic potential of targeting the YY1-AKT interaction.
Main Methods:
- Tissue microarray analysis of breast cancer samples.
- Cell culture experiments.
- Protein interaction mapping and domain analysis.
- Peptide inhibition assays.
Main Results:
- YY1 expression positively correlates with AKT(S473) phosphorylation in breast cancer.
- YY1 directly interacts with AKT via its oncogene protein binding (OPB) domain, promoting mTORC2-mediated phosphorylation.
- A peptide based on the OPB domain inhibits YY1-AKT interaction, reduces AKT phosphorylation, and decreases cell proliferation.
- YY1 expression is negatively associated with distant metastasis-free survival in breast cancer patients.
Conclusions:
- YY1 promotes AKT activation through direct interaction with AKT via the OPB domain, leading to increased mTORC2 access.
- Disrupting the YY1-AKT interaction using OPB domain-based peptides is a promising therapeutic strategy for cancer.
- YY1-mediated AKT activation is a critical driver of breast cancer progression and metastasis.
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