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SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression

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 rol...

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Autores principales: Wang, Lixia, Lin, Min, Chu, Man, Liu, Yi, Ma, Jia, He, Youhua, Wang, Zhi-wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248661/
https://www.ncbi.nlm.nih.gov/pubmed/32460168
http://dx.doi.org/10.1016/j.ebiom.2020.102795
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author Wang, Lixia
Lin, Min
Chu, Man
Liu, Yi
Ma, Jia
He, Youhua
Wang, Zhi-wei
author_facet Wang, Lixia
Lin, Min
Chu, Man
Liu, Yi
Ma, Jia
He, Youhua
Wang, Zhi-wei
author_sort Wang, Lixia
collection PubMed
description 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: 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: 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: Our study provides evidence for a novel mechanism of SPOP in kidney cancer progression in part through promoting degradation of the LATS1 tumour suppressor.
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spelling pubmed-72486612020-05-29 SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression Wang, Lixia Lin, Min Chu, Man Liu, Yi Ma, Jia He, Youhua Wang, Zhi-wei EBioMedicine Research paper 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: 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: 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: Our study provides evidence for a novel mechanism of SPOP in kidney cancer progression in part through promoting degradation of the LATS1 tumour suppressor. Elsevier 2020-05-03 /pmc/articles/PMC7248661/ /pubmed/32460168 http://dx.doi.org/10.1016/j.ebiom.2020.102795 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Wang, Lixia
Lin, Min
Chu, Man
Liu, Yi
Ma, Jia
He, Youhua
Wang, Zhi-wei
SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression
title SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression
title_full SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression
title_fullStr SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression
title_full_unstemmed SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression
title_short SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression
title_sort spop promotes ubiquitination and degradation of lats1 to enhance kidney cancer progression
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248661/
https://www.ncbi.nlm.nih.gov/pubmed/32460168
http://dx.doi.org/10.1016/j.ebiom.2020.102795
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