SUMO5, a Novel Poly-SUMO Isoform, Regulates PML Nuclear Bodies

Sci Rep. 2016 May 23:6:26509. doi: 10.1038/srep26509.

Abstract

Promyelocytic leukemia nuclear bodies (PML-NBs) are PML-based nuclear structures that regulate various cellular processes. SUMOylation, the process of covalently conjugating small ubiquitin-like modifiers (SUMOs), is required for both the formation and the disruption of PML-NBs. However, detailed mechanisms of how SUMOylation regulates these processes remain unknown. Here we report that SUMO5, a novel SUMO variant, mediates the growth and disruption of PML-NBs. PolySUMO5 conjugation of PML at lysine 160 facilitates recruitment of PML-NB components, which enlarges PML-NBs. SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs. The acute promyelocytic leukemia oncoprotein PML-RARα blocks SUMO5 conjugation of PML, causing cytoplasmic displacement of PML and disruption of PML-NBs. Our work not only identifies a new member of the SUMO family but also reveals the mechanistic basis of the PML-NB life cycle in human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cloning, Molecular
  • Gene Expression Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • K562 Cells
  • Lysine / metabolism*
  • MCF-7 Cells
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / metabolism
  • Organ Specificity
  • Promyelocytic Leukemia Protein / chemistry
  • Promyelocytic Leukemia Protein / genetics*
  • Promyelocytic Leukemia Protein / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Sumoylation
  • Transcription Factors / metabolism
  • Ubiquitins / metabolism

Substances

  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Protein Isoforms
  • RNF4 protein, human
  • SUMO2 protein, human
  • SUMO3 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Ubiquitins
  • PML protein, human
  • Lysine