EDEM1 regulates ER-associated degradation by accelerating de-mannosylation of folding-defective polypeptides and by inhibiting their covalent aggregation

Olivari, Silvia; Calì, Tito; Salo, Kirsi E.H.; Paganetti, Paolo; Ruddock, Lloyd W.; Molinari, Maurizio

doi:10.1016/j.bbrc.2006.08.186

Cited by 163 publications

(161 citation statements)

References 44 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…EDEM1 presumably possesses mannosidase activity that trims the C branch of N-glycans on misfolded proteins; however, that activity is apparently not required for ERAD acceleration because mutant EDEM1 that lacks the putative active site for mannosidase is still able to accelerate ERAD (Hosokawa et al 2001(Hosokawa et al , 2006(Hosokawa et al , 2010bMolinari et al 2003;Oda et al 2003;Olivari et al 2006). EDEM2 also promotes ERAD, even though it has no enzymatic activity (Mast et al 2005;Olivari et al 2005).…”

Section: Recognition and Targetingmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) uses an elaborate surveillance system called the ER quality control (ERQC) system. The ERQC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded polypeptides through ER-associated degradation (ERAD) or autophagic degradation. This mechanism of ER protein surveillance is closely linked to redox and calcium homeostasis in the ER, whose balance is presumed to be regulated by a specific cellular compartment. The potential to modulate proteostasis and metabolism with chemical compounds or targeted siRNAs may offer an ideal option for the treatment of disease.

show abstract

Section: Recognition and Targetingmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

View full text Add to dashboard Cite

show abstract

“…Extensive trimming of mannose residues of the precursor oligosaccharide is an essential requirement for glycoprotein ERAD [57] and α1,2 ER mannosidase I was proposed to function as an ERAD timer in the quality control of glycoproteins [58][59][60], together with a family of ER degradation enhancing α-mannosidase-like proteins (EDEMs), [61][62][63][64][65].…”

Section: Eradmentioning

confidence: 99%

Genesis of ER stress in Huntington’s Disease

Shenkman

Eiger

Lederkremer

2015

Endoplasmic Reticulum Stress in Diseases

View full text Add to dashboard Cite

Recent research has identified ER stress as a major mechanism implicated in cytotoxicity in many neurodegenerative diseases, among them Huntington’s disease. This genetic disorder is of late-onset, progressive and fatal, affecting cognition and movement. There is presently no cure nor any effective therapy for the disease. This review focuses on recent findings that shed light on the mechanisms of the advent and development of ER stress in Huntington’s disease and on its implications, highlighting possible therapeutic avenues that are being or could be explored.

show abstract

“…Although C. elegans ER α mannosidases have not yet been characterized, the mammalian ER α mannosidase is potentially inhibited by deoxymannojirimycin and kifnensin. 42,43) Furthermore, it was recently reported that mammalian EDEMs, especially EDEM1 and EDEM3, have some α mannosidase activity, 44,45) which had been described as lectin like proteins without enzyme activity. 46 48) Therefore involvement of ER α mannosidases and EDEMs on FOS generation should be tested in the future.…”

Section: Elegans Does Not Have Cytosolic α-Mannosidasementioning

confidence: 99%

Enzymes Involved in Generation and Degradation of the Free Oligosaccharides in the Cytosol of Caenorhabditis elegans

Ashida¹,

Kato²,

Kawahara³

et al. 2009

J. Appl. Glycosci.

View full text Add to dashboard Cite

Free oligosaccharides (FOS) in the cytosol of eukaryotic cells are mainly generated during endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins. We characterized the enzymes involved in generation and degradation of FOS in the nematode Caenorhabditis elegans. 1) Peptide: N-glycanase (PNGase) from Caenorhabditis elegans, which releases FOS from misfolded glycoproteins in the cytosol, was shown to be a unique bifunctional enzyme having both deglycosylation and protein disulfide reductase activities. 2) Endo-β-N-acetylglucosaminidase was proven to release a single GlcNAc residue at the reducing end of FOS in vivo. 3) Luminal class 1 α-mannosidases, probably Golgi α-mannosidase I, was involved in generation of M5A isoform of Man5GlcNAc1 that is specific to C. elegans.

show abstract

EDEM1 regulates ER-associated degradation by accelerating de-mannosylation of folding-defective polypeptides and by inhibiting their covalent aggregation

Cited by 163 publications

References 44 publications

Protein Folding and Quality Control in the ER

Protein Folding and Quality Control in the ER

Genesis of ER stress in Huntington’s Disease

Enzymes Involved in Generation and Degradation of the Free Oligosaccharides in the Cytosol of Caenorhabditis elegans

Contact Info

Product

Resources

About