Editors' ChoiceCell Biology

PTEN Variations

Sci. Signal.  30 Jul 2013:
Vol. 6, Issue 286, pp. ec177
DOI: 10.1126/scisignal.2004550

The product of the tumor suppressor gene phosphate and tensin homolog on chromosome ten (PTEN) is a lipid and protein phosphatase that regulates important cellular processes, including growth, survival, and metabolism (see the Perspective by Leslie and Brunton). Although PTEN is best known for effects on the phosphatidylnositol 3-kinase (PI3K) signaling pathway, the PTEN protein is also found in the nucleus. Bassi et al. found that PTEN’s presence in the nucleus was regulated in response to covalent modification of the protein by SUMOylation and phosphorylation. Cells lacking nuclear PTEN showed increased sensitivity to DNA damage and underwent cell death if the PI3K pathway was also inhibited. Hopkins et al. discovered an alternative translation start site in human PTEN messenger RNA that allowed expression of a protein, PTEN-Long, with about 170 extra amino acids. The unusual enzyme was released from cells and then taken up into other cells. In a mouse tumor model, uptake of the enzyme inhibited the PI3K pathway and inhibited tumor growth.

C. Bassi, J. Ho, T. Srikumar, R. J. O. Dowling, C. Gorrini, S. J. Miller, T. W. Mak, B. G. Neel, B. Raught, V. Stambolic, Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science 341, 395–399 (2013). [Abstract] [Full Text]

B. D. Hopkins, B. Fine, N. Steinbach, M. Dendy, Z. Rapp, J. Shaw, K. Pappas, J. S. Yu, C. Hodakoski, S. Mense, J. Klein, S. Pegno, M.-L. Sulis, H. Goldstein, B. Amendolara, L. Lei, M. Maurer, J. Bruce, P. Canoll, H. Hibshoosh, R. Parsons, A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science 341, 399–402 (2013). [Abstract] [Full Text]

N. R. Leslie, V. G. Brunton, Where is PTEN? Science 341, 355–356 (2013). [Abstract] [Full Text]