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.
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.
GTEx Analysis Release V8dbGaP, Accession phs000424.v8.p2.
GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysisNucleic Acids Res, 10.1093/nar/gkz430.
- W Lee Kraus
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Anthony K. L. Leung
© 2021, Palavalli Parsons et al.
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