TY - JOUR TI - Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells AU - Palavalli Parsons, Lavanya H AU - Challa, Sridevi AU - Gibson, Bryan A AU - Nandu, Tulip AU - Stokes, MiKayla S AU - Huang, Dan AU - Lea, Jayanthi S AU - Kraus, W Lee A2 - Cole, Philip A A2 - Leung, Anthony KL A2 - Leung, Anthony KL A2 - Matic, Ivan VL - 10 PY - 2021 DA - 2021/01/21 SP - e60481 C1 - eLife 2021;10:e60481 DO - 10.7554/eLife.60481 UR - https://doi.org/10.7554/eLife.60481 AB - PARP-7 (TiPARP) is a mono(ADP-ribosyl) transferase whose protein 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. KW - adp-ribosylation KW - PARP-7 KW - ovarian cancer KW - chemical genetics KW - alpha-tubulin KW - transcriptome JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -