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UBTD1 is a mechano‐regulator controlling cancer aggressiveness
- Source :
- EMBO Reports, EMBO Reports, 2019, 20 (4), pp.e46570. ⟨10.15252/embr.201846570⟩, EMBO Reports, EMBO Press, 2019, 20 (4), pp.e46570. ⟨10.15252/embr.201846570⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- International audience; Ubiquitin domain-containing protein 1 (UBTD1) is highly evolutionary conserved and has been described to interact with E2 enzymes of the ubiquitin-proteasome system. However, its biological role and the functional significance of this interaction remain largely unknown. Here, we demonstrate that depletion of UBTD1 drastically affects the mechanical properties of epithelial cancer cells via RhoA activation and strongly promotes their aggressiveness. On a stiff matrix, UBTD1 expression is regulated by cell-cell contacts, and the protein is associated with β-catenin at cell junctions. Yes-associated protein (YAP) is a major cell mechano-transducer, and we show that UBTD1 is associated with components of the YAP degradation complex. Interestingly, UBTD1 promotes the interaction of YAP with its E3 ubiquitin ligase β-TrCP Consequently, in cancer cells, UBTD1 depletion decreases YAP ubiquitylation and triggers robust ROCK2-dependent YAP activation and downstream signaling. Data from lung and prostate cancer patients further corroborate the in cellulo results, confirming that low levels of UBTD1 are associated with poor patient survival, suggesting that biological functions of UBTD1 could be beneficial in limiting cancer progression.
- Subjects :
- RHOA
Cell
Regulator
Cell Cycle Proteins
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Mechanotransduction, Cellular
Biochemistry
0302 clinical medicine
Ubiquitin
Neoplasms
matrix stiffness
ROCK2
Insulin-Like Growth Factor I
beta Catenin
0303 health sciences
biology
Chemistry
Articles
Prognosis
3. Good health
Cell biology
Ubiquitin ligase
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Disease Progression
Disease Susceptibility
YAP
Protein Binding
Signal Transduction
[SDV.CAN]Life Sciences [q-bio]/Cancer
Protein Serine-Threonine Kinases
Models, Biological
UBTD1
03 medical and health sciences
Cell Adhesion
Genetics
medicine
Humans
Hippo Signaling Pathway
Ubiquitins
Molecular Biology
030304 developmental biology
Cancer
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
β‐TrCP
beta-Transducin Repeat-Containing Proteins
medicine.disease
Cancer cell
biology.protein
rhoA GTP-Binding Protein
Protein Processing, Post-Translational
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 1469221X and 14693178
- Database :
- OpenAIRE
- Journal :
- EMBO Reports, EMBO Reports, 2019, 20 (4), pp.e46570. ⟨10.15252/embr.201846570⟩, EMBO Reports, EMBO Press, 2019, 20 (4), pp.e46570. ⟨10.15252/embr.201846570⟩
- Accession number :
- edsair.doi.dedup.....a7f62fcac6e6e9da5d4ee5cd5444de63