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.
Tiberi
Luca
L
Department of Experimental Pathology, University of Bologna, via S. Giacomo 12, 40126 Bologna, Italy.
Faisal
Amir
A
Rossi
Matteo
M
Di Tella
Lucia
L
Franceschi
Claudio
C
Salvioli
Stefano
S
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