Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS-1 in response to endoplasmic reticulum stress.

Misfolding of proteins during endoplasmic reticulum (ER) stress results in the formation of cytotoxic aggregates. The ER-associated degradation pathway counteracts such aggregation through the elimination of misfolded proteins by the ubiquitin-proteasome system. We now show that SHP substrate-1 (SHPS-1), a transmembrane glycoprotein that regulates cytoskeletal reorganization and cell-cell communication, is ...
a physiological substrate for the Skp1-Cullin1-NFB42-Rbx1 (SCF(NFB42)) E3 ubiquitin ligase, a proposed mediator of ER-associated degradation. SCF(NFB42) mediated the polyubiquitination of immature SHPS-1 and its degradation by the proteasome. Ectopic expression of NFB42 both suppressed the formation of aggresome-like structures and the phosphorylation of the translational regulator eIF2alpha induced by overproduction of SHPS-1 as well as increased the amount of mature SHPS-1 at the cell surface. An NFB42 mutant lacking the F box domain had no such effects. Our results suggest that SCF(NFB42) regulates SHPS-1 biosynthesis in response to ER stress.
Mesh Terms:
Amino Acid Sequence, Antigens, Differentiation, Base Sequence, Cell Cycle Proteins, Cell Line, Cysteine Endopeptidases, DNA Primers, Endoplasmic Reticulum, Fluorescent Antibody Technique, Membrane Glycoproteins, Molecular Sequence Data, Multienzyme Complexes, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Neural Cell Adhesion Molecule L1, Proteasome Endopeptidase Complex, Receptors, Immunologic, S-Phase Kinase-Associated Proteins, Ubiquitin
J. Biol. Chem.
Date: Mar. 19, 2004
Download Curated Data For This Publication
207356
Switch View:
  • Interactions 10