A Secreted PTEN Phosphatase That Enters Cells to Alter Signaling and Survival
Science2013Vol. 341(6144), pp. 399–402
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Benjamin D. Hopkins, Barry Fine, Nicole Steinbach, Meaghan Dendy, Zachary Rapp, Jacquelyn Shaw, Kyrie Pappas, Jennifer S. Yu, Cindy Hodakoski, Sarah M. Mense, Joshua U. Klein, Sarah Pegno, Maria Luisa Sulis, Hannah E. Goldstein, Benjamin Amendolara, Lei Liang, Matthew Maurer, Jeffrey N. Bruce, Peter Canoll, Hanina Hibshoosh, Ramon Parsons
Abstract
Phosphatase and tensin homolog on chromosome ten (PTEN) is a tumor suppressor and an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified a 576-amino acid translational variant of PTEN, termed PTEN-Long, that arises from an alternative translation start site 519 base pairs upstream of the ATG initiation sequence, adding 173 N-terminal amino acids to the normal PTEN open reading frame. PTEN-Long is a membrane-permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized PI3K signaling and induced tumor cell death in vitro and in vivo. By providing a means to restore a functional tumor-suppressor protein to tumor cells, PTEN-Long may have therapeutic uses.