Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

Benharouga, Mohamed; Haardt, Martin; Kartner, Norbert; Lukacs, Gergely L.

Only 20-30% of the newly synthesized CFTR enters the secretory pathway after its ATP-dependent conformational maturation (Lukacs et al., 1994; Zhang et al., 1998) assisted by cytosolic and ER-resident chaperones (Yang et al., 1993; Pind et al., 1994; Loo et al., 1998; Meacham et al., 1999) . Processing of the high mannose type N-linked glycan to complex type oligosaccharides in the cis/medial Golgi region is reflected by a decreased electrophoretic mobility ( ‫ف‬ 180 kD), providing a convenient method to monitor the trafficking of the CFTR (Cheng et al., 1990; Lukacs et al., 1994; Ward and Kopito, 1994; Riordan, 1999) . Not only does the folded complex-glycosylated CFTR have a slow turnover in vivo ( t 1/2 Ͼ 12 h), but it also displays a conformation which is more resistant to proteolysis in vitro (Zhang et al., 1998) . The posttranslational folding or conformational maturation of CFTR is independent of ER to Golgi vesicular transport, implying that complex glycosylation is not a prerequisite to attain the native conformation (Lukacs et al., 1994; Ward and Kopito, 1994; Zhang et al., 1998) .