Identifying Family-Member-Specific Targets of Mono-ARTDs by Using a Chemical Genetics Approach

• DOI: 10.1016/j.celrep.2015.12.045
• Publication Date: 2016-01-07T18:45:34Z
• Authors: Ian Carter-O’Connell; Haihong Jin; Rory K. Morgan; Roko Zaja; Larry L. David; Ivan Ahel; Michael S. Cohen
• Keywords: Chemical genetics; Family member

ADP-ribosyltransferases (ARTD1–16) have emerged as major downstream effectors of NAD+ signaling in the cell. Most ARTDs (ARTD7 and 8, 10–12, 14–17) catalyze transfer a single unit ADP-ribose from to target proteins, process known mono-ADP-ribosylation (MARylation). Progress understanding cellular functions MARylation has been limited by inability identify direct targets for individual mono-ARTDs. Here, we engineered mono-ARTDs use an analog that is orthogonal wild-type ARTDs. We profiled MARylomes ARTD10 ARTD11 vitro, identifying isoform-specific revealing potential role nuclear pore complex biology. found targeting dependent on both its regulatory catalytic domains, which important implications how recognize their targets. anticipate our chemical genetic strategy will be generalizable all mono-ARTD family members based similarity domains.