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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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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. |
format | Online Article Text |
id | pubmed-7248661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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