ABSTRACT
The notch system represents a proteolysis-driven mechanism of signal transduction across the cell membrane, or a proteolytic switch, in a particularly clear form. The regulation of programmed cell death is one of their major functions, and for this purpose they are equipped with a sophisticated machinery of interacting proteins. Into the transmembrane fragment of notch thus generated, a second membrane-integrated protease, γ-secretase, makes a single cut. The major signaling proteins targeted include growth factors, growth factor receptors, and corresponding downstream signal-processing molecules. Under normal conditions, the receptors coupled with TRADD activate preferentially the nuclear factor kappa B pathway. Cell death is induced not only by endogenous signals reacting with death receptors but also by many other, rather heterogeneous, stimuli. During its development to the mature animal consisting of 959 somatic cells, exactly 131 cells undergo apoptosis under the control of 10 different cell death genes.
