| Product description |
SHC-transforming protein 1 (UniProt: P29353; also known as SHC-transforming protein 3, SHC-transforming protein A, Src homology 2 domain-containing-transforming protein C1, SH2 domain protein C1) is encoded by the SHC1 (also known as SHC, SHCA) gene (Gene ID: 6464) in human. p66Shc is a splice variant of p52Shc/p46Shc with a typical domain organization that is shared by all members of the Shc family of adaptor proteins. It has a phosphotyrosine binding domain, a collagen homology 1 region, and an SH2 domain. p66Shc is shown to be a downstream target of p53 and activated p53 induces its up-regulation by increasing its stability. p66Shc is suggested to be a genetic determinant of aging in mammals as its homozygous deletion is reported to delay senescence and prolong life span in mice. It regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Under conditions of excessive reactive oxygen species (ROS), p66Shc is phosphorylated on serine 36 by protein kinase C and is targeted to the mitochondrial intermembrane space where it serves as a redox enzyme by oxidizing cytochrome c and reducing oxygen to form ROS. In the absence of p66Shc, release of cytochrome c from mitochondria is impaired and apoptosome can only be activated if purified cytochrome c is supplied. p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. p66Shc is also shown to have a neuroprotective role in a murine model of multiple sclerosis. p66Shc knockout (p66-KO) mice develop typical signs of experimental autoimmune encephalomyelitis (EAE). (Ref.: Su, KG., et al. (2012). Eur. J. Neurosci. 35; 562-571; Orsini, F., et al. (2004). J. Biol. Chem. 279(24); 25689-25695). |
