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Identification of RNF168 as a PML nuclear body regulator

Kathy Shire1, Andrew I Wong1, Michael H Tatham2

  • 1Department of Molecular Genetics, University of Toronto, 1 Kings College Circle, Toronto, Ontario, Canada M5S 1A8.

Journal of Cell Science
|December 18, 2015
PubMed

Insights

RNF8 and RNF168 proteins regulate Promyelocytic Leukemia nuclear bodies (PML NBs). Depleting these proteins increases PML NBs, while overexpressing them decreases PML NBs, revealing novel regulatory roles.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Ubiquitination and SUMOylation Pathways

Background:

  • Promyelocytic leukemia (PML) protein is crucial for PML nuclear bodies (PML NBs), which regulate vital cellular processes.
  • The precise regulation of PML NB formation and stability is essential for cellular function.

Purpose of the Study:

  • To identify novel regulators of PML nuclear bodies (PML NBs) within the ubiquitin pathway.
  • To investigate the roles of RNF8 and RNF168 in the modulation of PML NB levels and protein modifications.

Main Methods:

  • Screening of an shRNA library targeting ubiquitin pathway proteins.
  • Analysis of PML NB levels and protein modifications upon RNF8 and RNF168 depletion or overexpression.
  • Biochemical assays to determine the binding preference of RNF168 for modified ubiquitin chains.

Main Results:

  • RNF8 and RNF168 were identified as negative regulators of PML NBs.
  • Depletion of RNF8 or RNF168 led to increased PML NB levels and protein content.
  • RNF168 binds to PML NBs and promotes PML ubiquitylation and SUMO2 modification.
  • RNF168 preferentially binds to hybrid SUMO2-ubiquitin chains.

Conclusions:

  • RNF8 and RNF168 play significant, previously unrecognized roles in regulating PML NBs.
  • RNF168 exhibits a novel preference for binding hybrid SUMO-ubiquitin chains, impacting PML modification.
Keywords:
PML nuclear bodiesRNF168RNF8SUMO

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