Frontiers in Cell and Developmental Biology (Jan 2021)
Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB
- 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
Affiliations
- Yue Liu
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China
- Yue Liu
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yue Liu
- Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Yue Liu
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Wenjuan Zhang
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shiwen Wang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China
- Shiwen Wang
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shiwen Wang
- Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Shiwen Wang
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Lili Cai
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yanyu Jiang
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yongfu Pan
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yupei Liang
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Jingrong Xian
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China
- Jingrong Xian
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Jingrong Xian
- Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Jingrong Xian
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Lijun Jia
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Lihui Li
- Longhua Hospital, Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Hu Zhao
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China
- Hu Zhao
- Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Hu Zhao
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- Yanmei Zhang
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China
- Yanmei Zhang
- Research Center on Aging and Medicine, Fudan University, Shanghai, China
- Yanmei Zhang
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China
- DOI
- https://doi.org/10.3389/fcell.2021.617134
- Journal volume & issue
-
Vol. 9
Abstract
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.
Keywords
