Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells
- University of Texas Southwestern Medical Center, United States
Abstract
PARP-7 (TiPARP) is a mono(ADP-ribosyl) transferase whose proteins substrates and biological activities are poorly understood. We observed that PARP7 mRNA levels are lower in ovarian cancer patient samples compared to non-cancerous tissue, but PARP-7 protein nonetheless contributes to several cancer-related biological endpoints in ovarian cancer cells (e.g., growth, migration). Global gene expression analyses in ovarian cancer cells subjected to PARP-7 depletion indicate biological roles for PARP-7 in cell-cell adhesion and gene regulation. To identify the MARylated substrates of PARP-7 in ovarian cancer cells, we developed an NAD+ analog-sensitive approach, which we coupled with mass spectrometry to identify the PARP-7 ADP-ribosylated proteome in ovarian cancer cells, including cell-cell adhesion and cytoskeletal proteins. Specifically, we found that PARP-7 MARylates α-tubulin to promote microtubule instability, which may regulate ovarian cancer cell growth and motility. In sum, we identified an extensive PARP-7 ADP-ribosylated proteome with important roles in cancer-related cellular phenotypes.
Data availability
The RNA-seq sets generated for this study can be accessed from the NCBI's Gene Expression Omnibus (GEO) repository (http://www.ncbi.nlm.nih.gov/geo/) using the superseries accession number GSE153395. The new mass spec data sets generated for these studies are available as supplemental data provided with this manuscript. They can also be accessed from the Spectrometry Interactive Virtual Environment (MassIVE) repository (https://massive.ucsd.edu/ProteoSAFe/static/massive.jsp) using accession number MSV000086611.
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GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysisNucleic Acids Res, 10.1093/nar/gkz430.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK069710)
- W Lee Kraus
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anthony K. L. Leung
Version history
- Received: June 27, 2020
- Accepted: January 20, 2021
- Accepted Manuscript published: January 21, 2021 (version 1)
- Version of Record published: February 12, 2021 (version 2)
Copyright
© 2021, Palavalli Parsons et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells
eLife 10:e60481.
https://doi.org/10.7554/eLife.60481
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