期刊
CELL DEATH AND DIFFERENTIATION
卷 26, 期 10, 页码 1970-1986出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41418-018-0268-3
关键词
-
资金
- National Natural Science Foundation of China [81730062, 81761128003, 31800148, 81871642]
- NIH [R01CA213275, R01CA177377, R01CA132637]
- Natural Science Foundation of Jiangsu Higher Education Institutions of China [18KJB310004]
- Natural Science Foundation of Jiangsu Province [BK20180084]
- Nanjing Medical University [KY101RC1710]
Kaposi's sarcoma (KS), a highly invasive and angiogenic tumor of endothelial spindle-shaped cells, is the most common AIDS-associated cancer caused by KS-associated herpesvirus (KSHV) infection. KSHV-encoded viral FLICE-inhibitory protein (vFLIP) is a viral oncogenic protein, but its role in the dissemination and angiogenesis of KSHV-induced cancers remains unknown. Here, we report that vFLIP facilitates cell migration, invasion, and angiogenesis by downregulating the SAP18-HDAC1 complex. vFLIP degrades SAP18 through a ubiquitin-proteasome pathway by recruiting E3 ubiquitin ligase TRIM56. Further, vFLIP represses HDAC1, a protein partner of SAP18, by inhibiting Nanog occupancy on the HDAC1 promoter. Notably, vFLIP impairs the interaction between the SAP18/HDAC1 complex and p65 subunit, leading to enhancement of p65 acetylation and NF-kappa B activation. Our data suggest a novel mechanism of vFLIP activation of the NF-kappa B by decreasing the SAP18/HDAC1 complex to promote the acetylation of p65 subunit, which contributes to vFLIP-induced activation of the NF-kappa B pathway, cell invasion, and angiogenesis. These findings advance our understanding of the mechanism of KSHV-induced pathogenesis, and providing a rationale for therapeutic targeting of the vFLIP/SAP18/HDAC1 complex as a novel strategy of AIDS-KS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据