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 retinoblastoma tumor suppressor gene is a negative regulator of cell growth and the retinoblastoma protein (pRb) exhibits anti-apoptotic function. We show that pRb is cleaved during apoptosis induced by either UV irradiation or anti-Fas antibody. Our studies implicate CPP32-like activity in the proteolytic cleavage of pRb. The kinetics of proteolytic cleavage of pRb during apoptosis differ from that observed for other cellular proteins, suggesting that the specific cleavage of pRb during apoptosis may be an important event.
Diederich
L
L
Institut de Biologie Structurale J.-P. Ebel, Grenoble, France.
Fotedar
A
A
Fotedar
R
R
D000906:Antibodies; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004249:DNA Damage; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000276:immunology
D000906:Antibodies; D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; D016160:Retinoblastoma Protein; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1