Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

TUMOUR SUPPRESSORS

SPOP mutations disrupt phase separation

Speckle-type POZ protein (SPOP) is the substrate-binding subunit of a cullin 3 (CUL3)-based E3 ubiquitin ligase complex and is commonly mutated in prostate cancer, as well as in other solid tumours. SPOP mutations block substrate recruitment and lead to the accumulation of various proto-oncogenic proteins, but how SPOP recruits substrates is not known. Bouchard, Otero et al. find that substrate binding is necessary for SPOP complexes to accumulate in membrane-less organelles formed by phase separation. Cancer-associated SPOP mutations disrupt SPOP–substrate co-localization and phase separation, thus reducing ubiquitylation and degradation of substrates. This better understanding of the molecular mechanisms involved in substrate accumulation in SPOP-mutant cells might inform the development of therapies for cancers driven by SPOP mutations.

References

Original article

  1. Bouchard, J. J., Otero, J. H. et al. Cancer mutations of the tumor suppressor SPOP disrupt the formation of active, phase-separated compartments. Mol. Cell 72, 19–36.e8 (2018)

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sarah Seton-Rogers.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Seton-Rogers, S. SPOP mutations disrupt phase separation. Nat Rev Cancer 18, 667 (2018). https://doi.org/10.1038/s41568-018-0066-8

Download citation

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing