Premium
The ubiquitin ligase adaptor SPOP in cancer
Author(s) -
Cuneo Matthew J.,
Mittag Tanja
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15056
Subject(s) - ubiquitin ligase , ubiquitin , signal transducing adaptor protein , carcinogenesis , biology , epigenetics , deubiquitinating enzyme , microbiology and biotechnology , cancer research , cancer , signal transduction , genetics , gene
The dysregulation of ubiquitin‐mediated proteasomal degradation has emerged as an important mechanism of pathogenesis in several cancers. The speckle‐type POZ protein (SPOP) functions as a substrate adaptor for the cullin3‐RING ubiquitin ligase and controls the cellular persistence of a diverse array of protein substrates in hormone signalling, epigenetic control and cell cycle regulation, to name a few. Mutations in SPOP and the resulting dysregulation of this proteostatic pathway play causative roles in the pathogenesis of prostate and endometrial cancers, whereas overexpression and mislocalization are associated with kidney cancer. Understanding the molecular mechanism of the normal function of SPOP as well as the cause of SPOP‐mediated oncogenesis is thus critical for eventual therapeutic targeting of SPOP and other related pathways. Here, we will review SPOP structure, function and the molecular mechanism of how this function is achieved. We will then review how mutations and protein mislocalization contribute to cancer pathogenesis and will provide a perspective on how SPOP may be targeted therapeutically.