SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression.
Animals
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cullin Proteins
/ metabolism
Disease Progression
Gene Expression Regulation, Neoplastic
HEK293 Cells
Half-Life
Humans
Kidney Neoplasms
/ genetics
Mice
Neoplasm Transplantation
Nuclear Proteins
/ genetics
Protein Serine-Threonine Kinases
/ metabolism
Proteolysis
Repressor Proteins
/ genetics
Ubiquitination
Degradation
Growth
Kidney
LATS1
SPOP
Ubiquitination
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
14
12
2019
revised:
26
04
2020
accepted:
27
04
2020
pubmed:
28
5
2020
medline:
13
4
2021
entrez:
28
5
2020
Statut:
ppublish
Résumé
Emerging evidence has demonstrated that SPOP functions as an oncoprotein in kidney cancer to promote tumorigenesis by ubiquitination-mediated degradation of multiple regulators of cellular proliferation and apoptosis. However, the detailed molecular mechanism underlying the oncogenic role of SPOP in kidney tumorigenesis remains elusive. Multiple approaches such as Co-IP, Transfection, RT-PCR, Western blotting, and animal studies were utilized to explore the role of SPOP in kidney cancer. Here we identified LATS1, a critical component of the Hippo tumour suppressor pathway, as a novel ubiquitin substrate of SPOP. We found that LATS1 interacted with Cullin3, and depletion of Cullin 3 upregulated the abundance of LATS1 largely via prolonging LATS1 protein half-life. Mechanistically, SPOP specifically interacted with LATS1, and promoted the poly-ubiquitination and subsequent degradation of LATS1 in a degron-dependent manner. As such, over-expression of SPOP promoted cell proliferation partly through regulating cell cycle distribution in kidney cancer cells. Furthermore, SPOP also promoted kidney cancer cell invasion via degrading LATS1. Our study provides evidence for a novel mechanism of SPOP in kidney cancer progression in part through promoting degradation of the LATS1 tumour suppressor.
Sections du résumé
BACKGROUND
BACKGROUND
Emerging evidence has demonstrated that SPOP functions as an oncoprotein in kidney cancer to promote tumorigenesis by ubiquitination-mediated degradation of multiple regulators of cellular proliferation and apoptosis. However, the detailed molecular mechanism underlying the oncogenic role of SPOP in kidney tumorigenesis remains elusive.
METHODS
METHODS
Multiple approaches such as Co-IP, Transfection, RT-PCR, Western blotting, and animal studies were utilized to explore the role of SPOP in kidney cancer.
FINDINGS
RESULTS
Here we identified LATS1, a critical component of the Hippo tumour suppressor pathway, as a novel ubiquitin substrate of SPOP. We found that LATS1 interacted with Cullin3, and depletion of Cullin 3 upregulated the abundance of LATS1 largely via prolonging LATS1 protein half-life. Mechanistically, SPOP specifically interacted with LATS1, and promoted the poly-ubiquitination and subsequent degradation of LATS1 in a degron-dependent manner. As such, over-expression of SPOP promoted cell proliferation partly through regulating cell cycle distribution in kidney cancer cells. Furthermore, SPOP also promoted kidney cancer cell invasion via degrading LATS1.
INTERPRETATION
CONCLUSIONS
Our study provides evidence for a novel mechanism of SPOP in kidney cancer progression in part through promoting degradation of the LATS1 tumour suppressor.
Identifiants
pubmed: 32460168
pii: S2352-3964(20)30170-5
doi: 10.1016/j.ebiom.2020.102795
pmc: PMC7248661
pii:
doi:
Substances chimiques
CUL3 protein, human
0
Cullin Proteins
0
Nuclear Proteins
0
Repressor Proteins
0
SPOP protein, human
0
LATS1 protein, human
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102795Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflict of interest.
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