MassIVE MSV000086611

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Substrate Identification Using a Chemical Genetics Approach Reveals a Role for PARP-7-Mediated MARylation in Controlling Microtubule Stability in Ovarian Cancer Cells

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Description

To identify the ADPRylated substrates that underlie PARP-7-mediated ovarian cancer cell phenotypes, we developed an NAD+ analog-sensitive approach for PARP-7 comprising a PARP-7 NAD+ binding pocket mutant (S563G) paired with the NAD+ analog 8-Bu(3-yne)T-NAD+. When coupled with mass spectrometry, this approach allowed us to identify the PARP-7 ADP-ribosylated proteome in ovarian cancer cells, including components of the cell-cell adhesion and cytoskeleton organization machinery. Specifically, we found that PARP-7 monoADPRylates alpha-tubulin to promote microtubule instability, which may play a key role in the regulating ovarian cancer cell growth and motility. Collectively, our results point to an extensive PARP-7 ADP-ribosylated proteome with important roles in cancer-related cellular phenotypes. [doi:10.25345/C5KN3G] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: OVCAR4 ; PARP-7 ; Ovarian Cancer

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Principal Investigators:
(in alphabetical order) 		W Lee Kraus, The University of Texas Southwestern Medical Center at Dallas, United States
Submitting User: leekraus
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