The SUMO-specific isopeptidase SENP2 is targeted to intracellular membranes via a predicted N-terminal amphipathic α-helix

Mol Biol Cell. 2018 Aug 1;29(15):1878-1890. doi: 10.1091/mbc.E17-07-0445. Epub 2018 Jun 6.

Abstract

Sumoylation regulates a wide range of essential cellular functions, many of which are associated with activities in the nucleus. Although there is also emerging evidence for the involvement of the small ubiquitin-related modifier (SUMO) at intracellular membranes, the mechanisms by which sumoylation is regulated at membranes is largely unexplored. In this study, we report that the SUMO-specific isopeptidase, SENP2, uniquely associates with intracellular membranes. Using in vivo analyses and in vitro binding assays, we show that SENP2 is targeted to intracellular membranes via a predicted N-terminal amphipathic α-helix that promotes direct membrane binding. Furthermore, we demonstrate that SENP2 binding to intracellular membranes is regulated by interactions with the nuclear import receptor karyopherin-α. Consistent with membrane association, biotin identification (BioID) revealed interactions between SENP2 and endoplasmic reticulum, Golgi, and inner nuclear membrane-associated proteins. Collectively, our findings indicate that SENP2 binds to intracellular membranes where it interacts with membrane-associated proteins and has the potential to regulate their sumoylation and membrane-associated functions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Nucleus / metabolism
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism*
  • Membrane Proteins / metabolism
  • Models, Biological
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins / metabolism
  • Protein Binding
  • Protein Isoforms / metabolism
  • Protein Structure, Secondary
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Structure-Activity Relationship
  • alpha Karyopherins / metabolism

Substances

  • Membrane Proteins
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins
  • Protein Isoforms
  • Small Ubiquitin-Related Modifier Proteins
  • alpha Karyopherins
  • Cysteine Endopeptidases
  • SENP2 protein, human