title: Selective targeting of proteins within secretory pathway for endoplasmic reticulum-associated degradation.
abstract: The endoplasmic reticulum-associated degradation (ERAD) is a cellular quality control mechanism to dispose of misfolded proteins of the secretory pathway via proteasomal degradation. SEL1L is an ER-resident protein that participates in identification of misfolded molecules as ERAD substrates, therefore inducing their ER-to-cytosol retrotranslocation and degradation. We have developed a novel class of fusion proteins, termed degradins, composed of a fragment of SEL1L fused to a target-specific binding moiety located on the luminal side of the ER. The target-binding moiety can be a ligand of the target or derived from specific mAbs. Here, we describe the ability of degradins with two different recognition moieties to promote degradation of a model target. Degradins recognize the target protein within the ER both in secretory and membrane-bound forms, inducing their degradation following retrotranslocation to the cytosol. Thus, degradins represent an effective technique to knock-out proteins within the secretory pathway with high specificity.
authors.affiliation: Molecular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Vecchi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Petris
authors.forename: Marco
authors.initials: M
authors.lastname: Bestagno
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Burrone
mesh_terms: D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D017510:Protein Folding; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D011993:Recombinant Fusion Proteins; C117384:SEL1L protein, human