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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ABSTRACT: 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.
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: W Lee Kraus
PROVIDER: MSV000086611 | MassIVE | Thu Dec 17 07:28:00 GMT 2020
REPOSITORIES: MassIVE
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