PROTEOLYTIC CLEAVAGE OF RETINOBLASTOMA PROTEIN UPON DNA-DAMAGE AND FAS-MEDIATED APOPTOSIS

Proteolytic cleavage of key cellular proteins by caspases (ICE, CPP32, and Ich-1/Nedd2) may be crucial to the apoptotic process. The retinob lastoma tumor suppressor gene is a negative regulator of cell growth a nd the retinoblastoma protein (pRb) exhibits anti-apoptotic function. We show that pRb is cleaved during apoptosis induced by either UV irra diation or anti-Fas antibody. Our studies implicate CPP32-like activit y in the proteolytic cleavage of pRb. The kinetics of proteolytic clea vage of pRb during apoptosis differ from that observed for other cellu lar proteins, suggesting that the specific cleavage of pRb during apop tosis may be an important event.