Identification of PARP-7 substrates reveals a role for marylation in microtubule control in Ovarian cancer cells

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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.

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Palavalli Parsons, L. H., Challa, S., Gibson, B. A., Nandu, T., Stokes, M. S., Huang, D., … Lee Kraus, W. (2021). Identification of PARP-7 substrates reveals a role for marylation in microtubule control in Ovarian cancer cells. ELife, 10, 1–61. https://doi.org/10.7554/eLife.60481

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