The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.
Cancer Mutations of the Tumor Suppressor SPOP Disrupt the Formation of Active, Phase-Separated Compartments
Open accessAbstract
Summary 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. Diseaseassociated 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.
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Metadata
- Authors
- Bouchard, J. J., Otero, J. H., Scott, D. C., Szulc, E., Martin, E. W., Sabri, N., Granata, D., Marzahn, M. R., Lindorff-Larsen, K., Salvatella, X., Schulman, B. A., & Mittag, T.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 72
- Issue
- 1
- Pages
- 19-36.e8
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2891024355
- Cited by
- 391
- References
- 94
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Bouchard, J. J., Otero, J. H., Scott, D. C., Szulc, E., Martin, E. W., Sabri, N., Granata, D., Marzahn, M. R., Lindorff-Larsen, K., Salvatella, X., Schulman, B. A., & Mittag, T. (2018). Cancer Mutations of the Tumor Suppressor SPOP Disrupt the Formation of Active, Phase-Separated Compartments. Molecular Cell. https://doi.org/10.1016/j.molcel.2018.08.027
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