Broad Institute of Harvard and MIT, Cambridge, United States; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States; Division of Medical Genetics, School of Medicine, University of California, San Diego, San Diego, United States; Moores Cancer Center, University of California, San Diego, San Diego, United States
Christian Berrios
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States; Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, United States
Miju Kim
Broad Institute of Harvard and MIT, Cambridge, United States; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States; Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, United States
Guillaume Adelmant
Department of Cancer Biology and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, United States; Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, United States
Huwate Yeerna
Division of Medical Genetics, School of Medicine, University of California, San Diego, San Diego, United States
Emily Damato
Broad Institute of Harvard and MIT, Cambridge, United States
Amanda Balboni Iniguez
Broad Institute of Harvard and MIT, Cambridge, United States; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, United States
Laurence Florens
Stowers Institute for Medical Research, Kansas City, United States
Stowers Institute for Medical Research, Kansas City, United States; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, United States
Kim Stegmaier
Broad Institute of Harvard and MIT, Cambridge, United States; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, United States
Department of Cancer Biology and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, United States
Pablo Tamayo
Division of Medical Genetics, School of Medicine, University of California, San Diego, San Diego, United States; Moores Cancer Center, University of California, San Diego, San Diego, United States
Ole Gjoerup
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States
Jarrod A Marto
Department of Cancer Biology and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, United States; Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, United States
James DeCaprio
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States; Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, United States; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, United States
Broad Institute of Harvard and MIT, Cambridge, United States; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, United States
Alterations involving serine-threonine phosphatase PP2A subunits occur in a range of human cancers, and partial loss of PP2A function contributes to cell transformation. Displacement of regulatory B subunits by the SV40 Small T antigen (ST) or mutation/deletion of PP2A subunits alters the abundance and types of PP2A complexes in cells, leading to transformation. Here, we show that ST not only displaces common PP2A B subunits but also promotes A-C subunit interactions with alternative B subunits (B’’’, striatins) that are components of the Striatin-interacting phosphatase and kinase (STRIPAK) complex. We found that STRN4, a member of STRIPAK, is associated with ST and is required for ST-PP2A-induced cell transformation. ST recruitment of STRIPAK facilitates PP2A-mediated dephosphorylation of MAP4K4 and induces cell transformation through the activation of the Hippo pathway effector YAP1. These observations identify an unanticipated role of MAP4K4 in transformation and show that the STRIPAK complex regulates PP2A specificity and activity.
