DOI: 10.1073/pnas.96.23.13050. Regulation of the dolichol pathway in human fibroblasts by the endoplasmic reticulum unfolded protein response

Regulation of the dolichol pathway in human fibroblasts by the endoplasmic reticulum unfolded protein response

10.1073/pnas.96.23.13050

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells triggers the unfolded protein response (UPR), which activates transcription of several genes encoding ER chaperones and folding enzymes. This study reports that conversion of dolichol-linked Man 2–5 GlcNAc 2 intermediates into mature Glc 3 Man 9 GlcNAc 2 oligosaccharides in primary human adult dermal fibroblasts is also stimulated by the UPR. This stimulation was not evident in several immortal cell lines and did not require a cytoplasmic stress response. Inhibition of dolichol-linked Glc 3 Man 9 GlcNAc 2 synthesis by glucose deprivation could be counteracted by the UPR, improving the transfer of Glc 3 Man 9 GlcNAc 2 to asparagine residues on nascent polypeptides. Glycosidic processing of asparagine-linked Glc 3 Man 9 GlcNAc 2 in the ER leads to the production of monoglucosylated oligosaccharides that promote interaction with the lectin chaperones calreticulin and calnexin. Thus, control of the dolichol-linked Glc 3 Man 9 GlcNAc 2 supply gives the UPR the potential to maintain efficient protein folding in the ER without new synthesis of chaperones or folding enzymes.

Bibliography

Doerrler, W. T., & Lehrman, M. A. (1999). Regulation of the dolichol pathway in human fibroblasts by the endoplasmic reticulum unfolded protein response. Proceedings of the National Academy of Sciences, 96(23), 13050â13055.

Authors 2

William T. Doerrler (first)
Mark A. Lehrman (additional)

References 50 Referenced 41

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:41 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:37 p.m.)
Indexed	1 year, 1 month ago (July 17, 2024, 12:35 a.m.)
Issued	25 years, 9 months ago (Nov. 9, 1999)
Published	25 years, 9 months ago (Nov. 9, 1999)
Published Online	25 years, 9 months ago (Nov. 9, 1999)
Published Print	25 years, 9 months ago (Nov. 9, 1999)

Funders 0

None

BibTeX

@article{Doerrler_1999, title={Regulation of the dolichol pathway in human fibroblasts by the endoplasmic reticulum unfolded protein response}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.23.13050}, DOI={10.1073/pnas.96.23.13050}, number={23}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Doerrler, William T. and Lehrman, Mark A.}, year={1999}, month=nov, pages={13050–13055} }

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