| Structural highlights
Function
CUE1_YEAST Component of the endoplasmic reticulum-associated protein degradation (ERAD) pathway. Recruits the soluble ubiquitin-conjugating enzyme UBC7 to the cytoplasmic face of the endoplasmic reticulum membrane where it functions in degradation of misfolded or regulated proteins localized in the endoplasmic reticulum (ER) lumen or membrane via the ubiquitin-proteasome system. Targets the E2 conjugating enzyme UBC7 to the DOA10 ubiquitin ligase complex, which is part of the ERAD-C pathway responsible for the rapid degradation of membrane proteins with misfolded cytoplasmic domains, and to the HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M). Has also a role in cold adaptation, perhaps through effects on sterol biosynthesis.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
Publication Abstract from PubMed
Ubiquitin conjugation is an essential process modulating protein function in eukaryotic cells. Surprisingly, little is known about how the progressive assembly of ubiquitin chains is managed by the responsible enzymes. Only recently has ubiquitin binding activity emerged as an important factor in chain formation. The Ubc7 activator Cue1 carries a ubiquitin binding CUE domain that substantially stimulates K48-linked polyubiquitination mediated by Ubc7. Our results from NMR-based analysis and in vitro ubiquitination reactions point out that two parameters accelerate ubiquitin chain assembly: the increasing number of CUE binding sites and the position of CUE binding within a growing chain. In particular, interactions with a ubiquitin moiety adjacent to the acceptor ubiquitin facilitate chain elongation. These data indicate a mechanism for ubiquitin binding in which Cue1 positions Ubc7 and the distal acceptor ubiquitin for rapid polyubiquitination. Disrupting this mechanism results in dysfunction of the ERAD pathway by a delayed turnover of substrates.
The CUE Domain of Cue1 Aligns Growing Ubiquitin Chains with Ubc7 for Rapid Elongation.,von Delbruck M, Kniss A, Rogov VV, Pluska L, Bagola K, Lohr F, Guntert P, Sommer T, Dotsch V Mol Cell. 2016 Jun 16;62(6):918-28. doi: 10.1016/j.molcel.2016.04.031. Epub 2016 , Jun 2. PMID:27264873[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Biederer T, Volkwein C, Sommer T. Role of Cue1p in ubiquitination and degradation at the ER surface. Science. 1997 Dec 5;278(5344):1806-9. PMID:9388185
- ↑ Kopski KM, Huffaker TC. Suppressors of the ndc10-2 mutation: a role for the ubiquitin system in Saccharomyces cerevisiae kinetochore function. Genetics. 1997 Oct;147(2):409-20. PMID:9335582
- ↑ Lenk U, Sommer T. Ubiquitin-mediated proteolysis of a short-lived regulatory protein depends on its cellular localization. J Biol Chem. 2000 Dec 15;275(50):39403-10. PMID:10991948 doi:http://dx.doi.org/10.1074/jbc.M006949200
- ↑ Gilon T, Chomsky O, Kulka RG. Degradation signals recognized by the Ubc6p-Ubc7p ubiquitin-conjugating enzyme pair. Mol Cell Biol. 2000 Oct;20(19):7214-9. PMID:10982838
- ↑ Friedlander R, Jarosch E, Urban J, Volkwein C, Sommer T. A regulatory link between ER-associated protein degradation and the unfolded-protein response. Nat Cell Biol. 2000 Jul;2(7):379-84. PMID:10878801 doi:http://dx.doi.org/10.1038/35017001
- ↑ Walter J, Urban J, Volkwein C, Sommer T. Sec61p-independent degradation of the tail-anchored ER membrane protein Ubc6p. EMBO J. 2001 Jun 15;20(12):3124-31. PMID:11406589 doi:http://dx.doi.org/10.1093/emboj/20.12.3124
- ↑ Gardner RG, Shearer AG, Hampton RY. In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. Mol Cell Biol. 2001 Jul;21(13):4276-91. PMID:11390656 doi:10.1128/MCB.21.13.4276-4291.2001
- ↑ McBratney S, Winey M. Mutant membrane protein of the budding yeast spindle pole body is targeted to the endoplasmic reticulum degradation pathway. Genetics. 2002 Oct;162(2):567-78. PMID:12399372
- ↑ Carvalho P, Goder V, Rapoport TA. Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 2006 Jul 28;126(2):361-73. PMID:16873066 doi:10.1016/j.cell.2006.05.043
- ↑ Loertscher J, Larson LL, Matson CK, Parrish ML, Felthauser A, Sturm A, Tachibana C, Bard M, Wright R. Endoplasmic reticulum-associated degradation is required for cold adaptation and regulation of sterol biosynthesis in the yeast Saccharomyces cerevisiae. Eukaryot Cell. 2006 Apr;5(4):712-22. PMID:16607018 doi:http://dx.doi.org/10.1128/EC.5.4.712-722.2006
- ↑ Liao M, Faouzi S, Karyakin A, Correia MA. Endoplasmic reticulum-associated degradation of cytochrome P450 CYP3A4 in Saccharomyces cerevisiae: further characterization of cellular participants and structural determinants. Mol Pharmacol. 2006 Jun;69(6):1897-904. Epub 2006 Mar 23. PMID:16556771 doi:http://dx.doi.org/10.1124/mol.105.021816
- ↑ von Delbruck M, Kniss A, Rogov VV, Pluska L, Bagola K, Lohr F, Guntert P, Sommer T, Dotsch V. The CUE Domain of Cue1 Aligns Growing Ubiquitin Chains with Ubc7 for Rapid Elongation. Mol Cell. 2016 Jun 16;62(6):918-28. doi: 10.1016/j.molcel.2016.04.031. Epub 2016 , Jun 2. PMID:27264873 doi:http://dx.doi.org/10.1016/j.molcel.2016.04.031
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