p66(Shc) gene has a pro-apoptotic role in human cell lines and it is activated by a p53-independent pathway.
p66(Shc) protein has been proposed to be an indispensable factor for p53-dependent, mitochondria-mediated apoptosis in mice. Here, we show that p66(Shc) plays a pro-apoptotic role also in cell lines of human origin such as SaOs-2 and HeLa, where p53 is either absent or inactivated, thus, suggesting that p66(Shc) pro-apoptotic role is independent from the presence of a functional form of p53. The active form of p66(Shc) is phosphorylated in Serine 36. We confirm the importance of Serine 36 phosphorylation for p66(Shc) pro-apoptotic role, and our results suggest that the kinase involved in this process is activated independently from p53.
Department of Experimental Pathology, University of Bologna, via S. Giacomo 12, 40126 Bologna, Italy.
Luca
L
Tiberi
Amir
A
Faisal
Matteo
M
Rossi
Lucia
L
Di Tella
Claudio
C
Franceschi
Stefano
S
Salvioli
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D019943:Amino Acid Substitution / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D012694:Serine / Q000235:genetics / Q000502:physiology; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000235:genetics; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D016159:Tumor Suppressor Protein p53; D012694:Serine; D006861:Hydrogen Peroxide