SPOP Regulates the Nuclear Pore Protein NupJ

Abstract

Cell processes like growth and division are tightly regulated. One such mechanism of regulation is ubiquitination. Ubiquitination can change a protein's localization or activity, or it can mark the protein for degradation by the ubiquitin proteasome system. The final step of ubiquitination, the transfer of ubiquitin to the target protein, is mediated by E3 ubiquitin ligases and their substrate adaptors, proteins that allow E3 ligases to be selective in choosing their targets. Understanding the targets of E3 ligases and substrate adaptors, then, is crucial to understanding cell regulation and disease mechanisms linked to misregulation of protein levels and activity. SPOP is a Cul3 E3 ubiquitin ligase substrate adaptor whose targets, such as c‐Myc, PD‐L1, and ERG, are crucial for cell cycle progression and cancer proliferation. Through a mass spectrometry screen, we identified SPOP as a potential regulator of NupJ, a nuclear pore protein. Nuclear pore proteins play canonical roles in transport across the nuclear envelope and emerging roles in nuclear envelope morphology and cell division. SPOP and NupJ both co‐localize at the nuclear envelope via immunofluorescence microscopy, and co‐immunoprecipitation experiments demonstrate that SPOP and NupJ bind to each other in vitro and from cell lysates. Similar to overexpression of NupJ, siRNA against SPOP leads to an increase in the number of nuclear envelope defects. Moreoever, overexpressed NupJ leads to defects in cell division. Our results suggest that SPOP regulates NupJ activity and perhaps protein stability of NupJ.Support or Funding InformationJYO is supported by Edwin W. Pauley Fellowship, NSF Graduate Research Fellowship DGE‐1650604, and Ruth L. Kirschstein National Research Service Award GM007185. This work was funded by NSF MCB1243645 (to JZT).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.