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

Jacqueline Goeres, Pak Kei Chan, Debaditya Mukhopadhyay, Hong Zhang, Brian Raught, Michael J Matunis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4868-4882
Number of pages15
JournalMolecular Biology of the Cell
Volume22
Issue number24
DOIs
StatePublished - Dec 15 2011

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Nuclear Pore Complex Proteins
Karyopherins
Nuclear Pore
Cell Nucleus Active Transport
SUMO-1 Protein
Nuclear Export Signals
Fluorescence Recovery After Photobleaching
Nuclear Localization Signals
Ubiquitin
Mammals
Peptide Hydrolases
Yeasts
isopeptidase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The SUMO-specific isopeptidase SENP2 associates dynamically with nuclear pore complexes through interactions with karyopherins and the Nup107-160 nucleoporin subcomplex. / Goeres, Jacqueline; Chan, Pak Kei; Mukhopadhyay, Debaditya; Zhang, Hong; Raught, Brian; Matunis, Michael J.

In: Molecular Biology of the Cell, Vol. 22, No. 24, 15.12.2011, p. 4868-4882.

Research output: Contribution to journalArticle

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