A Secreted PTEN Phosphatase That Enters Cells to Alter Signaling and Survival

Abstract

PTEN Variations 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 ). Though 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. (p. 395 ) 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. (p. 399 , published online 6 June) 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.