The human E3 ligase RNF185 is a regulator of the SARS-CoV-2 envelope protein
Charles Zou,
Hojong Yoon,
Paul M.C. Park,
J.J. Patten,
Jesse Pellman,
Jeannie Carreiro,
Jonathan M. Tsai,
Yen-Der Li,
Shourya S. Roy Burman,
Katherine A. Donovan,
Jessica Gasser,
Adam S. Sperling,
Radosław P. Nowak,
Eric S. Fischer,
Robert A. Davey,
Benjamin L. Ebert,
Mikołaj Słabicki
Affiliations
Charles Zou
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Hojong Yoon
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Paul M.C. Park
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
J.J. Patten
Department of Microbiology, Boston University School of Medicine and NEIDL, Boston University, Boston, MA 02118, USA
Jesse Pellman
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Jeannie Carreiro
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Jonathan M. Tsai
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Yen-Der Li
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Shourya S. Roy Burman
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Katherine A. Donovan
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Jessica Gasser
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Adam S. Sperling
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Radosław P. Nowak
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Eric S. Fischer
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Robert A. Davey
Department of Microbiology, Boston University School of Medicine and NEIDL, Boston University, Boston, MA 02118, USA
Benjamin L. Ebert
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA; Corresponding author
Mikołaj Słabicki
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Corresponding author
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks multiple human proteins during infection and viral replication. To examine whether any viral proteins employ human E3 ubiquitin ligases, we evaluated the stability of SARS-CoV-2 proteins with inhibition of the ubiquitin proteasome pathway. Using genetic screens to dissect the molecular machinery involved in the degradation of candidate viral proteins, we identified human E3 ligase RNF185 as a regulator of protein stability for the SARS-CoV-2 envelope protein. We found that RNF185 and the SARS-CoV-2 envelope co-localize to the endoplasmic reticulum (ER). Finally, we demonstrate that the depletion of RNF185 significantly increases SARS-CoV-2 viral titer in a cellular model. Modulation of this interaction could provide opportunities for novel antiviral therapies.
