The SUMO-specific isopeptidase SENP2 associates dynamically with nuclear pore complexes through interactions with karyopherins and the Nup107-160 nucleoporin subcomplex

Mol Biol Cell. 2011 Dec;22(24):4868-82. doi: 10.1091/mbc.E10-12-0953. Epub 2011 Oct 26.

Abstract

The association of small, ubiquitin-related modifier-specific isopeptidases (also known as sentrin-specific proteases, or SENPs) with nuclear pore complexes (NPCs) is conserved in eukaryotic organisms ranging from yeast to mammals. However, the functional significance of this association remains poorly understood, particularly in mammalian cells. In this study, we have characterized the molecular basis for interactions between SENP2 and NPCs in human cells. Using fluorescence recovery after photobleaching, we demonstrate that SENP2, although concentrated at the nuclear basket, is dynamically associated with NPCs. This association is mediated by multiple targeting elements within the N-terminus of SENP2 that function cooperatively to mediate NPC localization. One of these elements consists of a high-affinity nuclear localization signal that mediates indirect tethering to FG-repeat-containing nucleoporins through karyopherins. A second element mediates interactions with the Nup107-160 nucleoporin subcomplex. A third element consists of a nuclear export signal. Collectively, our findings reveal that SENP2 is tethered to NPCs through a complex interplay of interactions with nuclear import and export receptors and nucleoporins. Disruption of these interactions enhances SENP2 substrate accessibility, suggesting an important regulatory node in the SUMO pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Amino Acid Motifs
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Nuclear Localization Signals / genetics
  • Nuclear Localization Signals / metabolism*
  • Nuclear Pore / genetics
  • Nuclear Pore / metabolism*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism

Substances

  • Karyopherins
  • Multiprotein Complexes
  • NUP107 protein, human
  • NUP160 protein, human
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • SUMO-1 Protein
  • Cysteine Endopeptidases
  • SENP2 protein, human