CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9
Abstract As a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression, but its biological functions and molecular mechanisms in melanoma remain unknown. Our study showed th...
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doaj-d60bb3dcbe36436188c5b255f000a3652021-01-24T12:04:53ZengNature Publishing GroupCell Death and Disease2041-48892021-01-0112111210.1038/s41419-021-03398-0CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9Yanli Zhang0Jianbing Hou1Shaomin Shi2Juan Du3Yudong Liu4Pan Huang5Qian Li6Lichao Liu7Huanrong Hu8Yacong Ji9Leiyang Guo10Yaqiong Shi11Yaling Liu12Hongjuan Cui13Department of Dermatology, The Third Hospital of Hebei Medical UniversityState Key Laboratory of Silkworm Genome Biology, Southwest UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityState Key Laboratory of Silkworm Genome Biology, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityDepartment of Dermatology, The Third Hospital of Hebei Medical UniversityState Key Laboratory of Silkworm Genome Biology, Southwest UniversityAbstract As a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression, but its biological functions and molecular mechanisms in melanoma remain unknown. Our study showed that CSN6 expression was upregulated in melanoma patients and cells, and correlated with poor survival in melanoma patients. In melanoma cells, CSN6 knockdown remarkably inhibited cell proliferation, tumorigenicity, migration, and invasion, whereas CSN6 recovery rescued the proliferative and metastatic abilities. Notably, we identified that CSN6 stabilized CDK9 expression by reducing CDK9 ubiquitination levels, thereby activating CDK9-mediated signaling pathways. In addition, our study described a novel CSN6-interacting E3 ligase UBR5, which was negatively regulated by CSN6 and could regulate the ubiquitination and degradation of CDK9 in melanoma cells. Furthermore, in CSN6-knockdown melanoma cells, UBR5 knockdown abrogated the effects caused by CSN6 silencing, suggesting that CSN6 activates the UBR5/CDK9 pathway to promote melanoma cell proliferation and metastasis. Thus, this study illustrates the mechanism by which the CSN6-UBR5-CDK9 axis promotes melanoma development, and demonstrate that CSN6 may be a potential biomarker and anticancer target in melanoma.https://doi.org/10.1038/s41419-021-03398-0 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yanli Zhang Jianbing Hou Shaomin Shi Juan Du Yudong Liu Pan Huang Qian Li Lichao Liu Huanrong Hu Yacong Ji Leiyang Guo Yaqiong Shi Yaling Liu Hongjuan Cui |
spellingShingle |
Yanli Zhang Jianbing Hou Shaomin Shi Juan Du Yudong Liu Pan Huang Qian Li Lichao Liu Huanrong Hu Yacong Ji Leiyang Guo Yaqiong Shi Yaling Liu Hongjuan Cui CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 Cell Death and Disease |
author_facet |
Yanli Zhang Jianbing Hou Shaomin Shi Juan Du Yudong Liu Pan Huang Qian Li Lichao Liu Huanrong Hu Yacong Ji Leiyang Guo Yaqiong Shi Yaling Liu Hongjuan Cui |
author_sort |
Yanli Zhang |
title |
CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 |
title_short |
CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 |
title_full |
CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 |
title_fullStr |
CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 |
title_full_unstemmed |
CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 |
title_sort |
csn6 promotes melanoma proliferation and metastasis by controlling the ubr5-mediated ubiquitination and degradation of cdk9 |
publisher |
Nature Publishing Group |
series |
Cell Death and Disease |
issn |
2041-4889 |
publishDate |
2021-01-01 |
description |
Abstract As a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression, but its biological functions and molecular mechanisms in melanoma remain unknown. Our study showed that CSN6 expression was upregulated in melanoma patients and cells, and correlated with poor survival in melanoma patients. In melanoma cells, CSN6 knockdown remarkably inhibited cell proliferation, tumorigenicity, migration, and invasion, whereas CSN6 recovery rescued the proliferative and metastatic abilities. Notably, we identified that CSN6 stabilized CDK9 expression by reducing CDK9 ubiquitination levels, thereby activating CDK9-mediated signaling pathways. In addition, our study described a novel CSN6-interacting E3 ligase UBR5, which was negatively regulated by CSN6 and could regulate the ubiquitination and degradation of CDK9 in melanoma cells. Furthermore, in CSN6-knockdown melanoma cells, UBR5 knockdown abrogated the effects caused by CSN6 silencing, suggesting that CSN6 activates the UBR5/CDK9 pathway to promote melanoma cell proliferation and metastasis. Thus, this study illustrates the mechanism by which the CSN6-UBR5-CDK9 axis promotes melanoma development, and demonstrate that CSN6 may be a potential biomarker and anticancer target in melanoma. |
url |
https://doi.org/10.1038/s41419-021-03398-0 |
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