Cul3 substrate adaptor SPOP targets Nup153 for degradation

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.