puc-header

A Protein Acyltransferase Complex Promotes Nonapoptotic Cell Death

47 Pages Posted: 17 Jun 2019 Sneak Peek Status: Review Complete

See all articles by Pin-Joe Ko

Pin-Joe Ko

Stanford University - Department of Biology

Claire Woodrow

Stanford University

Michael Dubreuil

Stanford University

Brent Martin

University of Michigan

Rachid Skouta

University of Massachusetts Amherst

Michael Bassik

Stanford University

Scott J. Dixon

Stanford University - Department of Biology

More...

Abstract

Lethal small molecules are useful probes to discover and characterize novel cell death pathways and biochemical mechanisms. Here we report that the synthetic oxime caspase-independent lethal 56 (CIL56) induces an unconventional form of nonapoptotic cell death distinct from necroptosis, ferroptosis and classic necrosis. CIL56-induced cell death requires a protein acyltransferase complex comprising the enzyme ZDHHC5 and an accessory subunit, GOLGA7, that is mutually stabilizing and localizes to the plasma membrane. ZDHHC5 activity is not required for CIL56 uptake into the cell, but rather promotes cell death in the context of CIL56 treatment, which inhibits protein secretion from the trans-Golgi apparatus. These results define a novel PAT complex that regulates an unconventional form of nonapoptotic cell death in response to compound treatment.

Keywords: Nonapoptotic cell death, palmitoylation, ZDHHC5

Suggested Citation

Ko, Pin-Joe and Woodrow, Claire and Dubreuil, Michael and Martin, Brent and Skouta, Rachid and Bassik, Michael and Dixon, Scott J., A Protein Acyltransferase Complex Promotes Nonapoptotic Cell Death (June 14, 2019). CELL-CHEMICAL-BIOLOGY-D-19-00200. Available at SSRN: https://ssrn.com/abstract=3404260 or http://dx.doi.org/10.2139/ssrn.3404260
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Pin-Joe Ko

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Claire Woodrow

Stanford University

Stanford, CA 94305
United States

Michael Dubreuil

Stanford University

Stanford, CA 94305
United States

Brent Martin

University of Michigan

Rachid Skouta

University of Massachusetts Amherst

Department of Operations and Information Managemen
Amherst, MA 01003
United States

Michael Bassik

Stanford University

Stanford, CA 94305
United States

Scott J. Dixon (Contact Author)

Stanford University - Department of Biology ( email )

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
166
Downloads
9