Proapoptotic signals

Besch R, Poeck H, Hohenauer T, Senft D, Hacker G, Berking C, Homung V, Endres S, Ruzicka T, Rothenfusser S, Hartmann G (2009) Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest 119 2399-2411... 

D1 (10,17S-docosatriene) from DHA using tandem liquid chromatography-photodiode array-electrospray ionization-tandem mass spectrometry (LC-PDA-ESI-MS-MS)-based lipidomic analysis have been documented in ischemic brain [4] and retinal pigment epithelium [5], This new lipid is called neuroprotectin D1 (1) because of its neuro-protectiveproperties in brain ischemia-reperfusion [4] and in oxidative stress-challenged retinal pigment epithelial cells [5] (2) because of its potent ability to inactivate proapoptotic signaling (see apoptosis, Ch. 35) [5] and (3) because it is the first identified neuroprotective mediator derived from DHA. 

Tlie initiator caspases receive proapoptotic signals and initiate the activation of a caspase cascade. Tliey are activated by an interaction with a transmembrane receptor or by cytotoxic influences. A complex is thus formed known as the apoptosome (see 15.4). The effector caspases are activated by an upstream caspase via a cascade mechanism. They are the component that executes apoptosis, initiates degradation of central proteins and directs the cell to death. 

The above findings define a proapoptotic signaling pathway involving p73 and c-Abl. Unlike p53, p73 protein levels do not increase following genotoxic stress. Moreover, although c-Abl interacts with p53 in an irradiated cell, it does not phosphorylate p53 but still contributes to radiation-induced G arrest by a p53-dependent mechanism (Yuan et al., 1999). Although p73 is related to p53, p53 alone is the tumor suppressor. p73 protein as yet has not been localized immunohistochemically. 

Kher A, Meldrum KK, Hile KL, Wang M, Tsai BM, Turrentine MW, et al. Aprotinin improves kidney function and decreases tubular cell apoptosis and proapoptotic signaling after renal ischemia-reperfusion. J Thorac Cardiovasc Surg 2005 130 662-669. 

M. Wang, B.M.Tsai,A. Kher, L.B. Baker, G.M. Wairiuko, D.R. Meldrum, The role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia and reperfusion, Am. J. Physiol. 288(1), H221-226 (2005). 

The initiator caspases receive proapoptotic signals and initiate the activation of a caspase cascade. They are activated by assembly into a multiprotein complex, and they contain large prodomains responsible for this interaction. 

---