Matches in SemOpenAlex for { <https://semopenalex.org/work/W2135896978> ?p ?o ?g. }
- W2135896978 endingPage "3009" @default.
- W2135896978 startingPage "2994" @default.
- W2135896978 abstract "Mannose-6-phosphate (M6P) is an essential precursor for mannosyl glycoconjugates, including lipid-linked oligosaccharides (LLO; glucose(3)mannose(9)GlcNAc(2)-P-P-dolichol) used for protein N-glycosylation. In permeabilized mammalian cells, M6P also causes specific LLO cleavage. However, the context and purpose of this paradoxical reaction are unknown. In this study, we used intact mouse embryonic fibroblasts to show that endoplasmic reticulum (ER) stress elevates M6P concentrations, leading to cleavage of the LLO pyrophosphate linkage with recovery of its lipid and lumenal glycan components. We demonstrate that this M6P originates from glycogen, with glycogenolysis activated by the kinase domain of the stress sensor IRE1-α. The apparent futility of M6P causing destruction of its LLO product was resolved by experiments with another stress sensor, PKR-like ER kinase (PERK), which attenuates translation. PERK's reduction of N-glycoprotein synthesis (which consumes LLOs) stabilized steady-state LLO levels despite continuous LLO destruction. However, infection with herpes simplex virus 1, an N-glycoprotein-bearing pathogen that impairs PERK signaling, not only caused LLO destruction but depleted LLO levels as well. In conclusion, the common metabolite M6P is also part of a novel mammalian stress-signaling pathway, responding to viral stress by depleting host LLOs required for N-glycosylation of virus-associated polypeptides. Apparently conserved throughout evolution, LLO destruction may be a response to a variety of environmental stresses." @default.
- W2135896978 created "2016-06-24" @default.
- W2135896978 creator A5010360422 @default.
- W2135896978 creator A5015378855 @default.
- W2135896978 creator A5038812998 @default.
- W2135896978 creator A5053978466 @default.
- W2135896978 creator A5055538365 @default.
- W2135896978 creator A5055851463 @default.
- W2135896978 creator A5061915900 @default.
- W2135896978 creator A5064589552 @default.
- W2135896978 creator A5077198825 @default.
- W2135896978 creator A5077934127 @default.
- W2135896978 creator A5091100215 @default.
- W2135896978 date "2011-09-01" @default.
- W2135896978 modified "2023-09-27" @default.
- W2135896978 title "Mannose-6-phosphate regulates destruction of lipid-linked oligosaccharides" @default.
- W2135896978 cites W1486073735 @default.
- W2135896978 cites W1512092650 @default.
- W2135896978 cites W1523693806 @default.
- W2135896978 cites W1523963034 @default.
- W2135896978 cites W1549823484 @default.
- W2135896978 cites W1553589468 @default.
- W2135896978 cites W1603657431 @default.
- W2135896978 cites W1770672301 @default.
- W2135896978 cites W1963486952 @default.
- W2135896978 cites W1963561902 @default.
- W2135896978 cites W1975854213 @default.
- W2135896978 cites W1978674393 @default.
- W2135896978 cites W1979582828 @default.
- W2135896978 cites W1986128585 @default.
- W2135896978 cites W1986536654 @default.
- W2135896978 cites W1990136127 @default.
- W2135896978 cites W1991999080 @default.
- W2135896978 cites W2001123985 @default.
- W2135896978 cites W2001467419 @default.
- W2135896978 cites W2002439304 @default.
- W2135896978 cites W2004267509 @default.
- W2135896978 cites W2006673705 @default.
- W2135896978 cites W2007078899 @default.
- W2135896978 cites W2018557479 @default.
- W2135896978 cites W2024117285 @default.
- W2135896978 cites W2036810334 @default.
- W2135896978 cites W2040518239 @default.
- W2135896978 cites W2047887493 @default.
- W2135896978 cites W2048030072 @default.
- W2135896978 cites W2048551040 @default.
- W2135896978 cites W2054631447 @default.
- W2135896978 cites W2058232093 @default.
- W2135896978 cites W2062460786 @default.
- W2135896978 cites W2063683785 @default.
- W2135896978 cites W2077547154 @default.
- W2135896978 cites W2079493278 @default.
- W2135896978 cites W2080901528 @default.
- W2135896978 cites W2088577754 @default.
- W2135896978 cites W2089198803 @default.
- W2135896978 cites W2093340118 @default.
- W2135896978 cites W2095609513 @default.
- W2135896978 cites W2106203560 @default.
- W2135896978 cites W2108290825 @default.
- W2135896978 cites W2112286580 @default.
- W2135896978 cites W2113640303 @default.
- W2135896978 cites W2114921406 @default.
- W2135896978 cites W2119510088 @default.
- W2135896978 cites W2120969631 @default.
- W2135896978 cites W2121295782 @default.
- W2135896978 cites W2124106344 @default.
- W2135896978 cites W2127906377 @default.
- W2135896978 cites W2129192121 @default.
- W2135896978 cites W2132326949 @default.
- W2135896978 cites W2137176215 @default.
- W2135896978 cites W2142853998 @default.
- W2135896978 cites W2152708819 @default.
- W2135896978 cites W2155163967 @default.
- W2135896978 cites W2157515789 @default.
- W2135896978 cites W2159586070 @default.
- W2135896978 cites W2160000151 @default.
- W2135896978 cites W2161940388 @default.
- W2135896978 cites W2192080449 @default.
- W2135896978 cites W2258310211 @default.
- W2135896978 cites W2808507257 @default.
- W2135896978 cites W4242150291 @default.
- W2135896978 cites W62793449 @default.
- W2135896978 cites W942333054 @default.
- W2135896978 cites W2043339786 @default.
- W2135896978 doi "https://doi.org/10.1091/mbc.e11-04-0286" @default.
- W2135896978 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3164449" @default.
- W2135896978 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21737679" @default.
- W2135896978 hasPublicationYear "2011" @default.
- W2135896978 type Work @default.
- W2135896978 sameAs 2135896978 @default.
- W2135896978 citedByCount "28" @default.
- W2135896978 countsByYear W21358969782012 @default.
- W2135896978 countsByYear W21358969782013 @default.
- W2135896978 countsByYear W21358969782014 @default.
- W2135896978 countsByYear W21358969782015 @default.
- W2135896978 countsByYear W21358969782016 @default.
- W2135896978 countsByYear W21358969782018 @default.
- W2135896978 countsByYear W21358969782019 @default.