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Cul3 substrate adaptor SPOP targets Nup153 for degradation

Joseph Y Ong1, Jorge Z Torres1,2,3

  • 1Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Biorxiv : the Preprint Server for Biology
|June 9, 2023
PubMed

Insights

Speckle-type POZ protein (SPOP) targets Nuclear Pore Complex protein 153 (Nup153) for degradation, impacting cell proliferation. This discovery reveals a new role for SPOP in maintaining cellular homeostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Speckle-type POZ protein (SPOP) is a Cul3 substrate adaptor crucial for regulating proteins involved in cell growth and proliferation.
  • Dysregulation of SPOP is implicated in cancer progression, highlighting the importance of identifying its substrates to understand cell proliferation control.

Approach:

  • Identified Nuclear Pore Complex protein 153 (Nup153) as a novel SPOP substrate.
  • Investigated the binding interaction and cellular localization of SPOP and Nup153.
  • Utilized RNA interference (RNAi) to assess the effect of SPOP depletion on Nup153 stability.
  • Examined the impact of SPOP loss on the localization of Mad1, a spindle assembly checkpoint protein tethered by Nup153.

Key Points:

  • SPOP and Nup153 interact and colocalize at the nuclear envelope and nuclear foci.
  • Nup153 undergoes ubiquitylation and degradation mediated by wild-type SPOP, but not a substrate-binding deficient mutant.
  • SPOP depletion results in Nup153 stabilization.
  • Loss of SPOP enhances the nuclear envelope localization of Mad1.

Conclusions:

  • SPOP directly regulates the protein levels of Nup153.
  • This study expands the understanding of SPOP's role in protein and cellular homeostasis.
  • The SPOP-Nup153 interaction provides new insights into the regulation of nuclear pore complex function and cell proliferation.

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