SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins

Membrane and secretory proteins that fail to pass quality control in the endoplasmic reticulum are discharged into the cytosol and degraded by the proteasome. Many of the mammalian components involved in this process remain to be identified. We performed a biochemical search for proteins that intera...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 105; no. 34; pp. 12325 - 12330
Main Authors Mueller, Britta, Klemm, Elizabeth J, Spooner, Eric, Claessen, Jasper H, Ploegh, Hidde L
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 26.08.2008
National Acad Sciences
Subjects
Animals
Antibodies
Biological Sciences
Carrier Proteins
Cell Line
Cell lines
Cells
Cytosol
Endoplasmic reticulum
Enzymes
Glycoproteins - metabolism
HeLa cells
Human cytomegalovirus
Humans
Membrane Proteins
Mice
Multiprotein Complexes - chemistry
Multiprotein Complexes - physiology
Protein Folding
Proteins
Proteins - metabolism
Proteins - physiology
Transduction, Genetic
Ubiquitins
Yeasts
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Summary:Membrane and secretory proteins that fail to pass quality control in the endoplasmic reticulum are discharged into the cytosol and degraded by the proteasome. Many of the mammalian components involved in this process remain to be identified. We performed a biochemical search for proteins that interact with SEL1L, a protein that is part of the mammalian HRD1 ligase complex and involved in substrate recognition. SEL1L is crucial for dislocation of Class I major histocompatibility complex heavy chains by the human cytomegalovirus US11 protein. We identified AUP1, UBXD8, UBC6e, and OS9 as functionally important components of this degradation complex in mammalian cells, as confirmed by mutagenesis and dominant negative versions of these proteins.
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Author contributions: B.M., E.J.K., and H.L.P. designed research; B.M., E.J.K., E.S., and J.H.C. performed research; B.M. and E.J.K. contributed new reagents/analytic tools; B.M., E.J.K., and H.L.P. analyzed data; and B.M. and H.L.P. wrote the paper.
Communicated by Gerald R. Fink, Whitehead Institute for Biomedical Research, Cambridge, MA, June 4, 2008
B.M. and E.J.K. contributed equally to this work.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0805371105