STAT6 degradation and ubiquitylated TRIML2 are essential for activation of human oncogenic herpesvirus

Feng Gu, Chong Wang, Fang Wei, Yuyan Wang, Qing Zhu, Ling Ding, Wenjia Xu, Caixia Zhu, Cankun Cai, Zhikang Qian, Zhenghong Yuan, Erle Robertson, Qiliang Cai

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Aberrations in STAT6-mediated signaling are linked to the development of multiple cancer types. Increasing evidence has shown that activation of human oncogenic herpesvirus lytic replication is crucial for viral tumorigenesis. However, the role of STAT6 in herpesvirus lytic replication remains elusive. Here, by using Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model, we revealed that RTA, the master regulator of lytic replication, interacts with STAT6 and promotes lysine 48 (K48) and K63-linked ubiquitylation of STAT6 for degradation via the proteasome and lysosome systems. Moreover, degradation of STAT6 is dramatically associated with the increased ubiquitylated form of tripartite motif family like 2 (TRIML2, a tumor suppressor) for prolonged cell survival and virion production, which is also commonly observed in lytic activation of Epstein-Barr virus, herpes simplex virus 1 and cytomegalovirus. These results suggest that degradation of STAT6 is important for the lytic activation of KSHV and as such, may be an attractive therapeutic target.

Original languageEnglish (US)
Article numbere1007416
JournalPLoS pathogens
Volume14
Issue number12
DOIs
StatePublished - Dec 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Gu et al. http://creativecommons.org/licenses/by/4.0/.

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