title: Molecular mechanisms supporting a pathogenic role for human polyomavirus 6 small T antigen: Protein phosphatase 2A targeting and MAPK cascade activation.
abstract: BRAF inhibitors are highly effective therapies in treating a subset of melanomas but are associated with induction of secondary cutaneous squamous cell carcinoma (cSCC). Recently, Human Polyomavirus 6 (HPyV6) was found to actively express viral proteins in BRAF inhibitor-induced cSCCs; however, the specific cellular mechanisms by which HPyV6 may facilitate neoplastic cell growth require further investigation. The current study describes a novel pathogenic mechanism of action for HPyV6 small tumor (sT) antigen which involves binding to protein phosphatase 2A (PP2A) via its WFG motif and zinc binding sites. Our findings demonstrate an important role of HPyV6 sT for activation of PP2A's downstream oncogenic pathways (MEK/ERK/c-Jun), which may underlie the pathogenesis of BRAF inhibitor-induced neoplasms. J. Med. Virol. 89:742-747, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Dermatology, University of Texas Health Science Center, Houston, Texas.|Baylor College of Medicine, Houston, Texas.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Department of Dermatology, University of Texas Health Science Center, Houston, Texas.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Simonette
authors.affiliation: Department of Dermatology, University of Texas Health Science Center, Houston, Texas.|Baylor College of Medicine, Houston, Texas.
authors.forename: Harrison P
authors.initials: HP
authors.lastname: Nguyen
authors.affiliation: Department of Dermatology, University of Texas Health Science Center, Houston, Texas.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Rady
authors.affiliation: Department of Dermatology, University of Texas Health Science Center, Houston, Texas.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
mesh_terms: D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D020935:MAP Kinase Signaling System; D011120:Polyomavirus / Q000472:pathogenicity*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D054648:Protein Phosphatase 2 / Q000378:metabolism*
chemical_list: D000957:Antigens, Viral, Tumor; D054648:Protein Phosphatase 2
keywords: BRAF; Human polyomavirus 6 (HPyV6); MAPK; PP2A; inhibitor-induced cSCC; sT antigen