BAP1 suppresses tumor development by inducing ferroptosis upon SLC7A11 repression.
Yilei Zhang1, Li Zhuang1, Boyi Gan1
1Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Molecular & Cellular Oncology
|February 22, 2019
Summary
The tumor suppressor BAP1 (BRCA1-associated protein 1) inhibits tumor growth by promoting ferroptosis. It achieves this by repressing the cystine transporter SLC7A11, a key BAP1 target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- The tumor suppressor BRCA1-associated protein 1 (BAP1) functions as a deubiquitinase, removing histone 2A ubiquitination.
- The precise mechanisms by which BAP1 suppresses tumor development are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying BAP1-mediated tumor suppression.
- To identify critical targets of BAP1 involved in its tumor-suppressive functions.
Main Methods:
- Investigated the interaction between BAP1 and the cystine transporter SLC7A11.
- Assessed the role of BAP1 in regulating SLC7A11 expression.
- Examined the impact of BAP1-mediated SLC7A11 repression on ferroptosis induction and tumor growth.
Main Results:
- Identified solute carrier family 7 member 11 (SLC7A11) as a direct and critical target of BAP1.
- Demonstrated that BAP1 represses SLC7A11 expression.
- Showed that BAP1 promotes ferroptosis, a non-apoptotic form of cell death, by downregulating SLC7A11.
Conclusions:
- BAP1 suppresses tumor development by inducing ferroptosis through the repression of SLC7A11.
- This study reveals a novel mechanism of tumor suppression mediated by BAP1 via the ferroptosis pathway.
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