The p76(Rb) and p100(Rb) truncated forms of the Rb protein exert antagonistic roles on cell death regulation in human cell lines.
Several caspase-cleaved forms of the retinoblastoma protein have been described. Here, we compared the effect of full-length Rb versus the truncated p76(Rb) and p100(Rb) proteins on cell death regulation in five human cell lines. Interestingly, we observed that p76(Rb) triggers cell death in all tested cell lines and that p100(Rb) protects two cell lines against etoposide or TNF-alpha-induced cell death, whereas full-length Rb has no apoptotic effect. These results show that truncated forms of Rb can have specific activities in the regulation of cell death. They also suggest that caspase cleavage of Rb should not be simply assimilated to a degradation process. Finally, we show that cell death induced by p76(Rb) is Bax-dependent and is diminished by Bcl-2 overexpression or by caspase inhibition and that p100(Rb) could inhibit cell death by decreasing both p53 stability and caspase activity.
Le Floch
Nathalie
N
Université de Versailles/St Quentin-en-Yvelines, CNRS FRE3216, Laboratoire de génétique et biologie cellulaire/Ecole Pratique des Hautes Etudes, Laboratoire de génétique moléculaire et physiologique, 45 avenue des Etats-Unis, 78035 Versailles cedex, France.
Rincheval
Vincent
V
Ferecatu
Ioana
I
Ali-Boina
Rahamata
R
Renaud
Flore
F
Mignotte
Bernard
B
Vayssière
Jean-Luc
JL
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D055550:Protein Stability; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051025:bcl-Associated Death Protein; D020169:Caspases