s-linking T-cell receptors. In nerve tissue, two cell-surface proteins, TNF R1 and APO-1/Fas, induce apoptosis when they bind their ligands. The bcl-2 gene is an "apoptosis off" control. In 1992, Korsmeyer discovered that bcl-2 is the mammalian equivalent of ced-9, a worm anti-death gene (S.J. Korsmeyer, Blood, 80:879-86). The proto-oncogene is an apoptosis "brake" in the skin. The gene is expressed in the basal layers, where stem cells must divide to supply more cells. In the upper layers, lack of bcl-2 protein permits apoptosis, preventing tumor formation. The bcl-2 protein binds a protein called bax. The bcl-2/bax ratio is critical to a cell's fate. If bcl-2 is in excess, all available bax is bound, apoptosis is blocked, and the cell lives. If bax is in excess, all bcl-2 is bound, the brake is released, and the cell dies (Z. Oltvai, C. Milliman, S. Korsmeyer, Cell, 74:609-14, 1993). Certain viruses also have apoptosis brake genes. "This keeps the cell it infects from committing suicide," says Steller. Such genes are found in adenovirus, Epstein-Barr virus, African swine flu virus, and vaccinia. Apoptosis' ties to the number of cells in certain organs and tissues suggest applications in correcting medical problems stemming from particular cellular excess or deficiency. "We've always thought of cancer as a proliferative process. Now there's a whole new way of thinking--the absence of cell death sets the stage for proliferation," says Buja. Kamb foresees applying knowledge about apoptosis to monitoring cancer treatment: "If you give chemotherapy that works through the apoptotic pathway, and can show that the tumor is not apoptosis-competent, you'd know that you're just poisoning the patient. Paying attention to apoptosis competency in tumors, diagnostically and prognostically, may provide a way to tailor therapy." Ricki Lewis is a textbook author and science writer based in Scotia, N.Y.The Scientist, Vol 9 #3 p. 15 February 6, 1995; Cop...
