Polyomavirus small t antigen interacts with Yes-associated protein to regulate cell survival and differentiation

Justin H. Hwang, Arun T. Pores Fernando, Nathalie Faure, Shaida Andrabi, William C. Hahn, Brian S. Schaffhausen, Thomas M. Roberts

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Murine polyomavirus small t antigen (PyST) regulates cell cycle, cell survival, apoptosis, and differentiation and cooperates with middle T antigen (MT) to transform primary cells in vitro and in vivo. Like all polyomavirus T antigens, PyST functions largely via its interactions with host cell proteins. Here, we show that PyST binds both Yes-associated protein 1 (YAP1) and YAP2, integral parts of the Hippo signaling pathway, which is a subject of increasing interest in human cancer. The transcription factor TEAD, which is a known target of YAP, is also found in PyST complexes. PyST enhanced YAP association with protein phosphatase 2A (PP2A), leading to decreased YAP phosphorylation. PyST increased YAP levels by decreasing its degradation. This effect was mediated by a reduction in YAP association with β-transducin repeat protein (βTRCP), which is known to regulate YAP turnover in a phosphorylation-dependent manner. Genetic analysis has identified PyST mutants defective in YAP binding. These mutants demonstrated that YAP binding is important for PyST to block myoblast differentiation and to synergize with the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) to promote cell death in 3T3-L1 preadipocytes placed under differentiation conditions. In addition to YAP binding, both of these phenotypes require PyST binding to PP2A.

Original languageEnglish (US)
Pages (from-to)12055-12064
Number of pages10
JournalJournal of virology
Volume88
Issue number20
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Dive into the research topics of 'Polyomavirus small t antigen interacts with Yes-associated protein to regulate cell survival and differentiation'. Together they form a unique fingerprint.

Cite this