TY - JOUR TI - STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells AU - Kim, Jong Wook AU - Berrios, Christian AU - Kim, Miju AU - Schade, Amy E AU - Adelmant, Guillaume AU - Yeerna, Huwate AU - Damato, Emily AU - Iniguez, Amanda Balboni AU - Florens, Laurence AU - Washburn, Michael P AU - Stegmaier, Kim AU - Gray, Nathanael S AU - Tamayo, Pablo AU - Gjoerup, Ole AU - Marto, Jarrod A AU - DeCaprio, James AU - Hahn, William C A2 - Davis, Roger J A2 - Akhmanova, Anna VL - 9 PY - 2020 DA - 2020/01/08 SP - e53003 C1 - eLife 2020;9:e53003 DO - 10.7554/eLife.53003 UR - https://doi.org/10.7554/eLife.53003 AB - 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. KW - PP2A KW - STRIPAK KW - small t KW - transformation KW - MAP4K4 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -