ABSTRACT
As outlined earlier in chapter 4 BiP is a constitutively expressed lumenal Ca2+ binding protein of sarco/endoplasmic reticulum that constitutes about 5% of the protein content of ER lumen in mammalian cells (Shiu et al., 1977; Welch et al., 1983; Munro and Pelham, 1986; Lee, 1987, 1992; Macer and Koch, 1988; Welch, 1990, 1991, 1993; Villa et al., 1991, 1993a, b; Volpe et al., 1992a, b; Gething and Sambrook, 1992; Lis and Wu, 1993; Nori et al., 1993; Georgopoulos and Welch, 1993; Hendrick and Hartl, 1993; Haas, 1994; Becker and Craig, 1994; Morimoto et al., 1994a, b). BiP serves as a molecular chaperon in the folding and translocation of proteins in ER (Ellis and Vander Vies, 1991; Sanders and Schekman, 1992; Ellis, 1993; Hebert et al., 1995; Hartl, 1995, 1996; Gaut and Hendershot, 1995; Wei and Hendershot, 1996; Buchner, 1996; Ruddon and Bedows, 1997; Rassow et al., 1997). Although details of this mechanism are largely unknown, there is general agreement that BiP transiently binds to nascent polypeptides in the endoplasmic reticulum lumen and prevents their misfolding and aggregation by marking those regions of the proteins that could develop incorrect associations. The complexes between BiP and the nascent proteins can be dissociated in vitro by ATP, but not by nonhydrolysable ATP analogues; ADP stablizes the interactions (Munro and Pelham, 1986; Pelham, 1986; Kassenbrock and Kelby, 1989; flaherty et al., 1990, 1991; Liberek et al., 1991; Gaut and Hendershot, 1993; Blond-Elguindi et al., 1993; Palleros et al., 1993; Schmid et al., 1994; Wei et al., 1995; Wei and Hendershot, 1995; Ziegelhoffer et al, 1995; Hendershot et al., 1996; Vidal et al., 1996; Glick et al., 1997). The ATP required for the regulation of BiP activity is provided by an ATP-carrier that transports ATP from the cytoplasm into the endoplasmic reticulum (Capasso et al., 1989; Clairmont et al., 1992; Mayinger and Meyer, 1993; Guillen and Hirschberg, 1995; Mayinger et al., 1995; Hirschberg, 1996; Shoshan-Barmatz et al., 1996; Abeijon et al., 1997).
