[The BCL2 gene, prototype of a gene family that controls programmed cell death (apoptosis)]

The BCL2 gene is the most representative member of a family of genes that control cell homeostatic processes in the course of the developmental and adult life. Some members of the BCL2 family (bcl-2 alpha, bcl-xL) inhibit apoptosis, whereas some other (Bax, Bclxs) induce it. The biological activity of these proteins is dictated by: 1) their capacity to be integrated in specific membranes of the cytoplasm; 2) their ability to homo- or hetero-dimerize, due to the presence of two highly conserved domains which are a signature of this gene family. The bcl-2 protein exhibits two main biochemical properties: it acts in an antioxidant metabolic pathway aimed at eliminating oxygene free radicals that induce lesions in DNA, lipids and proteins; it modulates intracellular Ca++ fluxes. BCL2 (and presumably its congeners) interplay with other genes involved in the tight control of cell proliferation and programmed cell death (c-myc, p53). A more comprehensive view of BCL2 functions should benefit to cancer chemotherapy by improving rational approach of the antitumor drug mechanisms.