Bcl-w and Bcl-xL cDNAs in the sense and antisense orientations into the nuclei of BDNF-dependent nodose neurons and NGF-dependent trigeminal neurons at stages
نویسندگان
چکیده
Proteins of the Bcl2 family play a key role in controlling the activation of caspases, the proteases that dismantle the cell in programmed cell death (Adams and Cory, 1998; Korsmeyer, 1999; Vaux and Korsmeyer, 1999). Bcl2-related proteins fall into two groups that generally either repress apoptosis (Bcl2, Bcl-xL [Bcl2lL], Bcl-w [Bcl2l2], A1 and Mcl1) or promote apoptosis (Bax, Bcl-xs [Bcl2ls], Bak, Bad, Bid, Bik [Biklk], Bok [Bokl-pending], Bim and Blk). (Symbols in square brackets are the nomenclature according to Mouse Genome Database.) Although it is not fully understood how they do this, there is growing evidence that some members of the Bcl2 family control the release of cytochrome c from mitochondria which promotes a cascade of caspase activation by interacting with the adapter protein Apaf1 which in turn activates procaspase-9 (Li et al., 1997b; Qin et al., 1999). Pro-apoptotic members like Bax and Bak increase mitochondrial permeability allowing cytochrome c to pass into the cytosol, whereas anti-apoptotic members like Bcl2 and Bcl-xL prevent cytochrome c release (Kharbanda et al., 1997; Kluck et al., 1997; Yang et al., 1997; Shimizu et al., 1999). Inhibiting the release of cytochrome c from mitochondria cannot entirely account for the means by which Bcl2 and Bcl-xL prevent apoptosis because overexpression of these proteins can prevent apoptosis in cells in which cytochrome c is present in the cytosol (Li et al., 1997a; Rosse et al., 1998). Bcl-xL can, however, promote cell survival by binding directly to Apaf1 and preventing it from activating pro-caspase-9 (Hu et al., 1998; Pan et al., 1998), and there is evidence that Bcl2 can regulate the activation of membrane-associated procaspase-3 independently of cytochrome c (Krebs et al., 1999). In addition to direct interaction with proteins of the survival/death machinery of the cell, it is known that members of the Bcl2 family can selectively heterodimerise and modulate one another’s function, suggesting that the ratio of pro-apoptotic to anti-apoptotic proteins in the cell governs whether it survives or dies (Korsmeyer et al., 1993). There is growing evidence that members of the Bcl2 family play important roles in regulating neuronal survival. Whereas overexpression of Bcl2 or Bcl-xL promote neuronal survival in vitro and in vivo (Garcia et al., 1992; Allsopp et al., 1993; Martinou et al., 1994; Farlie et al., 1995; Gonzalez-Garcia et al., 1995; Middleton et al., 1996; Parsadanian et al., 1998), reduction or elimination of endogenous Bcl2 or Bcl-xL reduces neuronal survival (Allsopp et al., 1995; Motoyama et al., 1995; Michaelidis et al., 1996; Piñón et al., 1997). In contrast, Bax overexpression accelerates neuronal death following 447 Development 128, 447-457 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV1584
منابع مشابه
Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development.
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