HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase

Author:

Chakraborty Abhishek A.1ORCID,Nakamura Eijiro1,Qi Jun1ORCID,Creech Amanda2ORCID,Jaffe Jacob D.2ORCID,Paulk Joshiawa1,Novak Jesse S.13,Nagulapalli Kshithija4,McBrayer Samuel K.1,Cowley Glenn S.2ORCID,Pineda Javier1,Song Jiaxi13,Wang Yaoyu E.4,Carr Steven A.2,Root David E.2,Signoretti Sabina13,Bradner James E.1ORCID,Kaelin William G.1256ORCID

Affiliation:

1. Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02215, USA.

2. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

3. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

4. Center for Cancer Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

5. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

6. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Abstract

Dysregulated H3K27 demethylase activity in pVHL-deficient cells increases dependence on the EZH1 H3K27 methyltransferase.

Funder

National Institutes of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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