title: Protein transport into the endoplasmic reticulum: mechanisms and pathologies.
abstract: Transport into the endoplasmic reticulum (ER) is the crucial step in the biosynthesis of most secretory proteins and many membrane proteins. The products of the SIL1, SEC62 and SEC63 genes act in concert with the SEC61 complex and the molecular chaperones BiP and GRP170 to transport proteins into the ER. Interestingly, recent genetic work has linked mutations in the human and murine SIL1 genes to neurodegeneration, and mutations in the human SEC63 gene to autosomal dominant polycystic liver disease. Furthermore, mutations in the SEC63 gene and overexpression of the SEC62 gene are associated with various human cancers. Therefore, we suggest that these diseases should be considered to be pathologies of protein transport into the ER rather than protein-folding diseases.
authors.affiliation: Medizinische Biochemie & Molekularbiologie and Klinik für Urologie & Kinderurologie, Universität des Saarlandes, D-66421 Homburg, Germany. bcrzim@uniklinikum-saarland.de
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Linda
authors.initials: L
authors.lastname: Müller
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018895:Microsatellite Repeats; D008954:Models, Biological; D018832:Molecular Chaperones; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D016601:RNA-Binding Proteins; D000069816:SEC Translocation Channels
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D016601:RNA-Binding Proteins; D000069816:SEC Translocation Channels; C487464:SEC63 protein, human; C418483:SIL1 protein, human