Activation of c-Jun by human cytomegalovirus UL42 through JNK activation

Abstract

c-Jun is a major component of the AP-1 transactivator complex. In this report, we demonstrated that AP-1 was activated by the expression of UL42, a human cytomegalovirus-encoded membrane protein that has two PPXY (PY) motifs and a C-terminal transmembrane domain (TMD). Although UL42 interacts with Itch, an ubiquitin E3 ligase, through the PY motifs, UL42 phosphorylated c-Jun and c-Jun N-terminal kinase (JNK) in the absence of any interaction with Itch. Experiments using mutated versions of UL42 suggest the importance of the carboxyl half (a.a. 52–124) of UL42 for the activation of the JNK signaling, while C-terminal TMD alone is not sufficient. Thus, we hypothesize that UL42 plays a role in the activation of JNK signaling in HCMV-infected cells. (118 words).