Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB
Rho family GTPase RhoB is the critical signaling component controlling the inflammatory response elicited by pro-inflammatory cytokines. However, the underlying mechanisms of RhoB degradation in inflammatory response remain unclear. In this study, for the first time, we identified that TNFAIP1, an a...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.617134/full |
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doaj-08ee2db298144d628f244db7f43202cd2021-01-21T07:50:14ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-01-01910.3389/fcell.2021.617134617134Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoBYue Liu0Yue Liu1Yue Liu2Yue Liu3Wenjuan Zhang4Shiwen Wang5Shiwen Wang6Shiwen Wang7Shiwen Wang8Lili Cai9Yanyu Jiang10Yongfu Pan11Yupei Liang12Jingrong Xian13Jingrong Xian14Jingrong Xian15Jingrong Xian16Lijun Jia17Lihui Li18Hu Zhao19Hu Zhao20Hu Zhao21Yanmei Zhang22Yanmei Zhang23Yanmei Zhang24Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaResearch Center on Aging and Medicine, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaResearch Center on Aging and Medicine, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaResearch Center on Aging and Medicine, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaResearch Center on Aging and Medicine, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaResearch Center on Aging and Medicine, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, ChinaRho family GTPase RhoB is the critical signaling component controlling the inflammatory response elicited by pro-inflammatory cytokines. However, the underlying mechanisms of RhoB degradation in inflammatory response remain unclear. In this study, for the first time, we identified that TNFAIP1, an adaptor protein of Cullin3 E3 ubiquitin ligases, coordinated with Cullin3 to mediate RhoB degradation through ubiquitin proteasome system. In addition, we demonstrated that downregulation of TNFAIP1 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in TNFα-stimulated hepatocellular carcinoma cells through the activation of p38/JNK MAPK pathway via blocking RhoB degradation. Our findings revealed a novel mechanism of RhoB degradation and provided a potential strategy for anti-inflammatory intervention of tumors by targeting TNFAIP1-RhoB axis.https://www.frontiersin.org/articles/10.3389/fcell.2021.617134/fullRhoBCRL3sTNFAIP1inflammatory responseMAPK signaling |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yue Liu Yue Liu Yue Liu Yue Liu Wenjuan Zhang Shiwen Wang Shiwen Wang Shiwen Wang Shiwen Wang Lili Cai Yanyu Jiang Yongfu Pan Yupei Liang Jingrong Xian Jingrong Xian Jingrong Xian Jingrong Xian Lijun Jia Lihui Li Hu Zhao Hu Zhao Hu Zhao Yanmei Zhang Yanmei Zhang Yanmei Zhang |
| spellingShingle |
Yue Liu Yue Liu Yue Liu Yue Liu Wenjuan Zhang Shiwen Wang Shiwen Wang Shiwen Wang Shiwen Wang Lili Cai Yanyu Jiang Yongfu Pan Yupei Liang Jingrong Xian Jingrong Xian Jingrong Xian Jingrong Xian Lijun Jia Lihui Li Hu Zhao Hu Zhao Hu Zhao Yanmei Zhang Yanmei Zhang Yanmei Zhang Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB Frontiers in Cell and Developmental Biology RhoB CRL3s TNFAIP1 inflammatory response MAPK signaling |
| author_facet |
Yue Liu Yue Liu Yue Liu Yue Liu Wenjuan Zhang Shiwen Wang Shiwen Wang Shiwen Wang Shiwen Wang Lili Cai Yanyu Jiang Yongfu Pan Yupei Liang Jingrong Xian Jingrong Xian Jingrong Xian Jingrong Xian Lijun Jia Lihui Li Hu Zhao Hu Zhao Hu Zhao Yanmei Zhang Yanmei Zhang Yanmei Zhang |
| author_sort |
Yue Liu |
| title |
Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB |
| title_short |
Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB |
| title_full |
Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB |
| title_fullStr |
Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB |
| title_full_unstemmed |
Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB |
| title_sort |
cullin3-tnfaip1 e3 ligase controls inflammatory response in hepatocellular carcinoma cells via ubiquitination of rhob |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Cell and Developmental Biology |
| issn |
2296-634X |
| publishDate |
2021-01-01 |
| description |
Rho family GTPase RhoB is the critical signaling component controlling the inflammatory response elicited by pro-inflammatory cytokines. However, the underlying mechanisms of RhoB degradation in inflammatory response remain unclear. In this study, for the first time, we identified that TNFAIP1, an adaptor protein of Cullin3 E3 ubiquitin ligases, coordinated with Cullin3 to mediate RhoB degradation through ubiquitin proteasome system. In addition, we demonstrated that downregulation of TNFAIP1 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in TNFα-stimulated hepatocellular carcinoma cells through the activation of p38/JNK MAPK pathway via blocking RhoB degradation. Our findings revealed a novel mechanism of RhoB degradation and provided a potential strategy for anti-inflammatory intervention of tumors by targeting TNFAIP1-RhoB axis. |
| topic |
RhoB CRL3s TNFAIP1 inflammatory response MAPK signaling |
| url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.617134/full |
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