@article{c4abe9608fbf48d3a44504232a26a54d,
title = "Identifying Family-Member-Specific Targets of Mono-ARTDs by Using a Chemical Genetics Approach",
abstract = "ADP-ribosyltransferases (ARTD1-16) have emerged as major downstream effectors of NAD+ signaling in the cell. Most ARTDs (ARTD7 and 8, 10-12, and 14-17) catalyze the transfer of a single unit of ADP-ribose from NAD+ to target proteins, a process known as mono-ADP-ribosylation (MARylation). Progress in understanding the cellular functions of MARylation has been limited by the inability to identify the direct targets for individual mono-ARTDs. Here, we engineered mono-ARTDs to use an NAD+ analog that is orthogonal to wild-type ARTDs. We profiled the MARylomes of ARTD10 and ARTD11 in vitro, identifying isoform-specific targets and revealing a potential role for ARTD11 in nuclear pore complex biology. We found that ARTD11 targeting is dependent on both its regulatory and catalytic domains, which has important implications for how ARTDs recognize their targets. We anticipate that our chemical genetic strategy will be generalizable to all mono-ARTD family members based on the similarity of the mono-ARTD catalytic domains.",
author = "Ian Carter-O'Connell and Haihong Jin and Morgan, {Rory K.} and Roko Zaja and David, {Larry L.} and Ivan Ahel and Cohen, {Michael S.}",
note = "Funding Information: We thank John Klimek for assistance with the MS analysis at the OHSU proteomics core, Jeffrey Huang for assistance with immunofluorescence microscopy, and P. Chang for the GFP-ARTD10 construct. We thank the members of M.S.C.{\textquoteright}s lab for many helpful discussions regarding the manuscript and experimental design. This work was funded by the NIH (NIH 1R01NS088629) to M.S.C., and I.C.-O. was supported by a Postdoctoral Fellowship (PF-15-008-01-CDD) from the American Cancer Society. M.S.C., I.C.O., H.J., and R.K.M. are inventors on a provisional patent for the identification of direct mono-PARP targets. Funding Information: We thank John Klimek for assistance with the MS analysis at the OHSU proteomics core, Jeffrey Huang for assistance with immunofluorescence microscopy, and P. Chang for the GFP-ARTD10 construct. We thank the members of M.S.C.{\textquoteright}s lab for many helpful discussions regarding the manuscript and experimental design. This work was funded by the NIH (NIH 1R01NS088629) to M.S.C., and I.C.-O. was supported by a Postdoctoral Fellowship (PF-15-008-01-CDD) from the American Cancer Society. M.S.C., I.C.O., H.J., and R.K.M. are inventors on a provisional patent for the identification of direct mono-PARP targets.",
year = "2016",
month = jan,
day = "26",
doi = "10.1016/j.celrep.2015.12.045",
language = "English (US)",
volume = "14",
pages = "621--631",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}