Identification of PARP-7 Substrates Reveals a Role for MARylation in Microtubule Control in Ovarian Cancer Cells

Overview

Journal Elife

Specialty Biology

Date 2021 Jan 21

PMID 33475085

Citations 35

Authors

Lavanya H Palavalli Parsons

Sridevi Challa

Bryan A Gibson

Tulip Nandu

MiKayla S Stokes

Dan Huang

Jayanthi S Lea

W Lee Kraus

Affiliations

Soon will be listed here.

Abstract

PARP-7 (TiPARP) is a mono(ADP-ribosyl) transferase whose protein substrates and biological activities are poorly understood. We observed that 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.

Citing Articles

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