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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
PubMed

Insights

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.
Keywords:
BAP1H2A ubiquitinationSLC7A11ferroptosismetabolismtumor suppression

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