Profibrillin-1 maturation by human dermal fibroblasts: proteolytic processing and molecular chaperones.

Autor: Wallis DD; Department of Internal Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA., Putnam EA, Cretoiu JS, Carmical SG, Cao SN, Thomas G, Milewicz DM
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2003 Oct 15; Vol. 90 (3), pp. 641-52.
DOI: 10.1002/jcb.10657
Abstrakt: Fibrillin-1 is synthesized as a proprotein that undergoes proteolytic processing in the unique C-terminal domain by a member of the PACE/furin family of endoproteases. This family of endoproteases is active in the trans-Golgi network (TGN), but metabolic labeling studies have been controversial as to whether profibrillin-1 is processed intracellularly or after secretion. This report provides evidence that profibrillin-1 processing is not an intracellular event. Bafilomycin A(1) and incubation of dermal fibroblasts at 22 degrees C were used to block secretion in the TGN to confirm that profibrillin-1 processing did not occur in this compartment. Profibrillin-1 immunoprecipitation studies revealed that two endoplasmic reticulum-resident molecular chaperones, BiP and GRP94, interacted with profibrillin-1. To determine the proprotein convertase responsible for processing profibrillin-1, a specific inhibitor of furin, alpha-1-antitrypsin, Portland variant, was both expressed in the cells and added to cells exogenously. In both cases, the inhibitor blocked the processing of profibrillin-1, providing evidence that furin is the enzyme responsible for profibrillin-1 processing. These studies delineate the secretion and proteolytic processing of profibrillin-1, and identify the proteins that interact with profibrillin-1 in the secretory pathway.
(Copyright 2003 Wiley-Liss, Inc.)
Databáze: MEDLINE
Externí odkaz: