Biochemical and molecular mechanisms regulating apoptosis.

In eukaryotes, the regulation of tissue cell numbers is a critical homeostatic objective that is achieved through tight control of apoptosis, mitosis and differentiation. While much is known about the genetic regulation of cell growth and differentiation, the molecular basis of apoptosis is less well understood. Genes involved in both cell proliferation and apoptosis reflect the role of some stimuli in both of these processes, the cell response depending on the overall cellular milieu. Recent research has given fascinating insights into the complex genetic and molecular mechanisms regulating apoptosis. A picture is emerging of the initiation in certain cells, after an apoptotic trigger, of sequential gene expression and specific signal transduction cascades that guide cells along the cell death pathway. Changes in gene expression precede the better known biochemical and morphological changes of apoptosis. It seems possible that, as a result of increased understanding of the cellular events preceding cell death, apoptosis may become more amenable to manipulation by appropriate drug- and gene-based therapies.