During acute disease, the promyelocytic leukemia (PML) protein becomes fused to another protein as a result of a chromosomal translocation. This protein appears to have multiple and varied functions, including the ability to form distinctive complexes in the nucleus that suppress tumorigenesis and promote apoptotic cell death. Giorgi et al. (see the Perspective by Culjkovic-Kraljacic and Borden) have proposed a mechanism by which PML influences the cellular signals that promote apoptosis. The protein was localized at sites of contact between the endoplasmic reticulum and mitochondria, where it associated with a calcium channel, a protein kinase, and a protein phosphatase, to regulate calcium mobilization into the mitochondrion, which then triggers the cell death program.
C. Giorgi, K. Ito, H.-K. Lin, C. Santangelo, M. R. Wieckowski, M. Lebiedzinska, A. Bononi, M. Bonora, J. Duszynski, R. Bernardi, R. Rizzuto, C. Tacchetti, P. Pinton, P. P. Pandolfi, PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330, 1247–1251 (2010). [Abstract] [Full Text]