title: Actin-dependent activation of serum response factor in T cells by the viral oncoprotein tip.
abstract: Serum response factor (SRF) acts as a multifunctional transcription factor regulated by mutually exclusive interactions with ternary complex factors (TCFs) or myocardin-related transcription factors (MRTFs). Binding of Rho- and actin-regulated MRTF:SRF complexes to target gene promoters requires an SRF-binding site only, whereas MAPK-regulated TCF:SRF complexes in addition rely on flanking sequences present in the serum response element (SRE). Here, we report on the activation of an SRE luciferase reporter by Tip, the viral oncoprotein essentially contributing to human T-cell transformation by Herpesvirus saimiri. SRE activation in Tip-expressing Jurkat T cells could not be attributed to triggering of the MAPK pathway. Therefore, we further analyzed the contribution of MRTF complexes. Indeed, Tip also activated a reporter construct responsive to MRTF:SRF. Activation of this reporter was abrogated by overexpression of a dominant negative mutant of the MRTF-family member MAL. Moreover, enrichment of monomeric actin suppressed the Tip-induced reporter activity. Further upstream, the Rho-family GTPase Rac, was found to be required for MRTF:SRF reporter activation by Tip. Initiation of this pathway was strictly dependent on Tip's ability to interact with Lck and on the activity of this Src-family kinase. Independent of Tip, T-cell stimulation orchestrates Src-family kinase, MAPK and actin pathways to induce SRF. These findings establish actin-regulated transcription in human T cells and suggest its role in viral oncogenesis.
authors.affiliation: Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. Brigitte.Biesinger@viro.med.uni-erlangen.de.
authors.forename: Kristin
authors.initials: K
authors.lastname: Katsch
authors.forename: Sarah Jill
authors.initials: SJ
authors.lastname: de Jong
authors.forename: Jens-Christian
authors.initials: JC
authors.lastname: Albrecht
authors.forename: Julia
authors.initials: J
authors.lastname: Steger
authors.forename: Harald
authors.initials: H
authors.lastname: Genth
authors.forename: Guido
authors.initials: G
authors.lastname: Posern
authors.forename: Brigitte
authors.initials: B
authors.lastname: Biesinger