Editors' ChoiceCell Biology

Promoting and Protecting From Cell Death

Science's STKE  04 Jan 2005:
Vol. 2005, Issue 265, pp. tw5
DOI: 10.1126/stke.2652005tw5

Mutations in the protein kinase Raf are frequently associated with human tumors. Raf functions in growth-promoting signaling and also acts to protect cells from apoptosis, a key event that allows cancer cells to avoid normal fail-safe mechanisms that stop uncontrolled cell growth. Surprisingly, Raf's protective effect against apoptosis appears not to require enzymatic activity of Raf. O'Neill et al. describe an interaction between Raf-1 and another protein kinase, MST2, in mammalian cells. Raf-1 appears to directly inhibit activation of MST2 in vitro, and this effect, like that of Raf-1 on apoptosis, was independent of catalytic activity of Raf-1. Cells lacking Raf-1 showed increased activity of MST2, which correlated with an increased propensity to undergo apoptosis. Decreased expression of MST2 protected cells from apoptosis. Thus, MST2 represents an important new target of Raf-1 that may help in the control of cell proliferation and cell death in normal and cancerous cells.

E. O'Neill, L. Rushworth, M. Baccarini, W. Kolch, Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science 306, 2267-2270 (2004). [Abstract] [Full Text]