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

Lavanya H. Palavalli Parsons, Sridevi Challa, Bryan A. Gibson, Tulip Nandu, Mikayla S. Stokes, Dan Huang, Jayanthi S. Lea, W. Lee Kraus

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere60481
Pages (from-to)1-61
Number of pages61
JournaleLife
Volume10
DOIs
StatePublished - Jan 2021

Keywords

  • ADP-ribosylation
  • Alpha-tubulin
  • Chemical biology
  • Chemical genetics
  • Mass spectrometry
  • Microtubules
  • NAD analog
  • Nicotinamide adenine dinucleotide (NAD)
  • Ovarian cancer
  • Poly(ADP-ribose) polymerase-7 (PARP-7)
  • TCDD-inducible PARP (TiPARP)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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