Activation Of STAT3-dependent transcription by herpesvirus saimiri STP C488

Abstract

Herpesvirus saimiri (HVS) is a member of the gamma subfamily of herpesviruses. HVS subgroup C strain 488(STP C488 oncoprotein)contains a divergent form of the STP gene along with an additional apparently unrelated open read frame in the left most position. Certain viruses modify STAT (especially STAT3) activity to increase the persistence, replication or oncogenic potential of the viruses. We now demonstrate that STP C488 activates STAT3-dependent transcription and STP C488 associates with STAT3. Point mutations that disrupted association with ras is not related to the STAT3-dependent transcriptional activity. STAT3 dependent transcriptional activity is not affected by MEKK 1-C and MEK-1. Expression of STP C488 with ERK activated the STAT3 dependent transcription up to 7-folds. Consistentent with an activation of signaling through ERK, STP C488 interacts with ERK1, 2 and STP C488 Recruits ERK1, 2 to the complex to bind with STAT3. Binding of STP C488 to ERK leads to activation of ERK serine/threonine kinase, and activated ERK triggers serine phosphorylation of STAT3, followed by STAT3 dependent transcriptional activation. ERK may represent an important mediators in the cellular signaling networks by STP C488.