A Ubc7p-binding Domain in Cue1p Activates ER-associated Protein Degradation

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2009 Apr 16

PMID 19366730

Citations 29

Authors

Zlatka Kostova

Jennifer Mariano

Simone Scholz

Carolin Koenig

Allan M Weissman

Affiliations

Soon will be listed here.

Abstract

Cue1p is an N-terminally anchored endoplasmic reticulum (ER) protein essential for the activity of the two major yeast RING finger ubiquitin ligases (E3s) implicated in ER-associated degradation (ERAD). Cue1p contains a CUE domain, which for several proteins is known to bind ubiquitin. We now establish that the CUE domain is dispensable for ERAD of substrates of both Hrd1p and Doa10p and that the Cue1p transmembrane domain is similarly not required for degradation of the Hrd1p substrate CPY. Cue1p interacts with the ERAD E2 Ubc7p in vivo. We show that a discrete C-terminal Ubc7p binding region (U7BR) of Cue1p is required for ERAD and for Ubc7p-dependent ubiquitylation by Hrd1p in vitro. Strikingly, when Ubc7p is stabilized by direct anchoring to the ER membrane, the U7BR is sufficient to restore ERAD in cells lacking Cue1p. Thus, discrete E2 binding sites independent of ubiquitin ligase domains have the potential to activate ubiquitylation.

Citing Articles

Ubiquiton-An inducible, linkage-specific polyubiquitylation tool.

Renz C, Asimaki E, Meister C, Albanese V, Petriukov K, Krapoth N Mol Cell. 2023; 84(2):386-400.e11.

PMID: 38103558 PMC: 10804999. DOI: 10.1016/j.molcel.2023.11.016.

Mechanisms of substrate processing during ER-associated protein degradation.

Christianson J, Jarosch E, Sommer T Nat Rev Mol Cell Biol. 2023; 24(11):777-796.

PMID: 37528230 DOI: 10.1038/s41580-023-00633-8.

A structurally conserved site in AUP1 binds the E2 enzyme UBE2G2 and is essential for ER-associated degradation.

Smith C, Tsai Y, Liang Y, Khago D, Mariano J, Li J PLoS Biol. 2021; 19(12):e3001474.

PMID: 34879065 PMC: 8699718. DOI: 10.1371/journal.pbio.3001474.

Who with whom: functional coordination of E2 enzymes by RING E3 ligases during poly-ubiquitylation.

Lips C, Ritterhoff T, Weber A, Janowska M, Mustroph M, Sommer T EMBO J. 2020; 39(22):e104863.

PMID: 33015833 PMC: 7667886. DOI: 10.15252/embj.2020104863.

Ubiquitination in the ERAD Process.

Lopata A, Kniss A, Lohr F, Rogov V, Dotsch V Int J Mol Sci. 2020; 21(15).

PMID: 32731622 PMC: 7432864. DOI: 10.3390/ijms21155369.

References

Kang R, Daniels C, Francis S, Shih S, Salerno W, Hicke L . Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding. Cell. 2003; 113(5):621-30. DOI: 10.1016/s0092-8674(03)00362-3. View

Taxis C, Vogel F, Wolf D . ER-golgi traffic is a prerequisite for efficient ER degradation. Mol Biol Cell. 2002; 13(6):1806-18. PMC: 117605. DOI: 10.1091/mbc.01-08-0399. View

Tsai Y, Mendoza A, Mariano J, Zhou M, Kostova Z, Chen B . The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nat Med. 2007; 13(12):1504-9. DOI: 10.1038/nm1686. View

Prag G, Misra S, Jones E, Ghirlando R, Davies B, Horazdovsky B . Mechanism of ubiquitin recognition by the CUE domain of Vps9p. Cell. 2003; 113(5):609-20. DOI: 10.1016/s0092-8674(03)00364-7. View

Christensen D, Brzovic P, Klevit R . E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages. Nat Struct Mol Biol. 2007; 14(10):941-8. DOI: 10.1038/nsmb1295. View

Meusser B, Hirsch C, Jarosch E, Sommer T . ERAD: the long road to destruction. Nat Cell Biol. 2005; 7(8):766-72. DOI: 10.1038/ncb0805-766. View

Taxis C, Hitt R, Park S, Deak P, Kostova Z, Wolf D . Use of modular substrates demonstrates mechanistic diversity and reveals differences in chaperone requirement of ERAD. J Biol Chem. 2003; 278(38):35903-13. DOI: 10.1074/jbc.M301080200. View

Hofmann R, Pickart C . Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell. 1999; 96(5):645-53. DOI: 10.1016/s0092-8674(00)80575-9. View

Huyer G, Piluek W, Fansler Z, Kreft S, Hochstrasser M, Brodsky J . Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble luminal protein. J Biol Chem. 2004; 279(37):38369-78. DOI: 10.1074/jbc.M402468200. View

10.

Gardner R, Shearer A, Hampton R . In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. Mol Cell Biol. 2001; 21(13):4276-91. PMC: 87088. DOI: 10.1128/MCB.21.13.4276-4291.2001. View

11.

Carvalho P, Goder V, Rapoport T . Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 2006; 126(2):361-73. DOI: 10.1016/j.cell.2006.05.043. View

12.

Lee J, Song B, DeBose-Boyd R, Ye J . Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. J Biol Chem. 2006; 281(51):39308-15. DOI: 10.1074/jbc.M608999200. View

13.

Nakatsukasa K, Brodsky J . The recognition and retrotranslocation of misfolded proteins from the endoplasmic reticulum. Traffic. 2008; 9(6):861-70. PMC: 2754126. DOI: 10.1111/j.1600-0854.2008.00729.x. View

14.

Song B, Sever N, DeBose-Boyd R . Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Mol Cell. 2005; 19(6):829-40. DOI: 10.1016/j.molcel.2005.08.009. View

15.

Gao B, Lee S, Chen A, Zhang J, Zhang D, Kannan K . Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen-induced arthritis. EMBO Rep. 2008; 9(5):480-5. PMC: 2373369. DOI: 10.1038/embor.2008.37. View

16.

Chen B, Mariano J, Tsai Y, Chan A, Cohen M, Weissman A . The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain, RING finger, and an E2-binding site. Proc Natl Acad Sci U S A. 2006; 103(2):341-6. PMC: 1326157. DOI: 10.1073/pnas.0506618103. View

17.

Plemper R, Deak P, Otto R, Wolf D . Re-entering the translocon from the lumenal side of the endoplasmic reticulum. Studies on mutated carboxypeptidase yscY species. FEBS Lett. 1999; 443(3):241-5. DOI: 10.1016/s0014-5793(98)01724-4. View

18.

Ravid T, Hochstrasser M . Autoregulation of an E2 enzyme by ubiquitin-chain assembly on its catalytic residue. Nat Cell Biol. 2007; 9(4):422-7. DOI: 10.1038/ncb1558. View

19.

Biederer T, Volkwein C, Sommer T . Role of Cue1p in ubiquitination and degradation at the ER surface. Science. 1997; 278(5344):1806-9. DOI: 10.1126/science.278.5344.1806. View

20.

Shih S, Prag G, Francis S, Sutanto M, Hurley J, Hicke L . A ubiquitin-binding motif required for intramolecular monoubiquitylation, the CUE domain. EMBO J. 2003; 22(6):1273-81. PMC: 151082. DOI: 10.1093/emboj/cdg140. View