AI Article Synopsis
- - Mutations in the tumor suppressor SPOP are linked to cancers like prostate and breast cancer, and these mutations disrupt its ability to interact with other proteins.
- - SPOP usually helps in assembling proteins in specific cellular structures called membraneless organelles, and this process is influenced by phase separation triggered by its substrates.
- - Cancer-related mutations in SPOP hinder its phase separation ability and mess with its function, leading to the accumulation of harmful proteins, which impacts protein regulation in the cell.
Article Abstract
Mutations in the tumor suppressor SPOP (speckle-type POZ protein) cause prostate, breast, and other solid tumors. SPOP is a substrate adaptor of the cullin3-RING ubiquitin ligase and localizes to nuclear speckles. Although cancer-associated mutations in SPOP interfere with substrate recruitment to the ligase, mechanisms underlying assembly of SPOP with its substrates in liquid nuclear bodies and effects of SPOP mutations on assembly are poorly understood. Here, we show that substrates trigger phase separation of SPOP in vitro and co-localization in membraneless organelles in cells. Enzymatic activity correlates with cellular co-localization and in vitro mesoscale assembly formation. Disease-associated SPOP mutations that lead to the accumulation of proto-oncogenic proteins interfere with phase separation and co-localization in membraneless organelles, suggesting that substrate-directed phase separation of this E3 ligase underlies the regulation of ubiquitin-dependent proteostasis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179159 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2018.08.027 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!