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Ubiquitin and proteasomes

Protein regulation by monoubiquitin

Key Points

  • Multi-ubiquitin chains target proteins for destruction by the proteasome. However, several proteins are monoubiquitylated. Recently, monoubiquitin has emerged as a regulator of the location and activity of diverse cellular proteins.

  • Histone regulation: Core histones H2A and H2B and the linker histone H1 are monoubiquitylated. Ubiquitylation of histones is important for gene expression during meiosis and development.

  • Endocytosis: Monoubiquitin serves as a signal to trigger the regulated internalization of plasma membrane proteins. Monoubiquitylation might also regulate the activity of components of the endocytic machinery.

  • Virus budding: The retrovirus Gag polyprotein is monoubiquitylated and this modification is required for late stages of virus budding from infected cells.

  • Surface regions of ubiquitin that are important for its different functions have been defined. One hydrophobic patch is promiscuous and is crucial for such diverse processes as proteasomal degradation and endocytosis. Another surface patch is important only for endocytosis and might have a role specifically in monoubiquitin functions.

  • Modification with monoubiquitin might regulate protein location and activity in ways that are similar to modification with the ubiquitin-like proteins, SUMO-1, Rub1 and Apg12.

  • Regulation of ubiquitin modification is important so that monoubiquitylated proteins are not inappropriately multi-ubiquitylated and degraded. Monoubiquitylation could be regulated by the activity of specific components of the ubiquitin machinery, by de-ubiquitylating enzymes, or by the presence or absence of positive and negative regulators of multi-ubiquitin chain assembly.

  • Many more monoubiquitin proteins probably exist and remain to be identified. The mechanism by which monoubiquitin regulates substrate protein location and activity is a mystery that is the next big challenge for researchers in the field.

Abstract

Multi-ubiquitin chains at least four subunits long are required for efficient recognition and degradation of ubiquitylated proteins by the proteasome, but other functions of ubiquitin have been discovered that do not involve the proteasome. Some proteins are modified by a single ubiquitin or short ubiquitin chains. Instead of sending proteins to their death through the proteasome, monoubiquitylation regulates processes that range from membrane transport to transcriptional regulation.

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Figure 1: Monoubiquitylation versus multi-ubiquitylation.
Figure 2: Monoubiquitylation of histones.
Figure 3: Roles of monoubiquitin during internalization of plasma membrane proteins into the endocytic pathway.
Figure 4: Monoubiquitylation of Gag is required for retrovirus budding.
Figure 5: Three-dimensional structure of ubiquitin.

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References

  1. Chau, V. et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243, 1576? 1583 (1989).

    Article  CAS  Google Scholar 

  2. Thrower, J. S., Hoffman, L., Rechsteiner, M. & Pickart, C. M. Recognition of the polyubiquitin proteolytic signal. EMBO J. 19, 94?102 (2000).

    Article  CAS  Google Scholar 

  3. Hochstrasser, M. Ubiquitin-dependent protein degradation. Annu. Rev. Genet. 30, 405?439 (1996).

    Article  CAS  Google Scholar 

  4. Voges, D., Zwickl, P. & Baumeister, W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu. Rev. Biochem. 68, 1015?1068 (1999).

    Article  CAS  Google Scholar 

  5. Galan, J. M. & Haguenauer-Tsapis, R. Ubiquitin Lys63 is involved in ubiquitination and endocytosis of a yeast plasma membrane protein. EMBO J. 16, 5847?5854 ( 1997).

    Article  CAS  Google Scholar 

  6. Terrell, J., Shih, S., Dunn, R. & Hicke, L. A function for monoubiquitination in the internalization of a G protein-coupled receptor. Mol. Cell 1, 193?202 ( 1998).This paper shows that monoubiquitylation on a single lysine residue is necessary and sufficient for rapid endocytosis of an activated signal-transducing receptor in yeast.

    Article  CAS  Google Scholar 

  7. Hofmann, R. M. & Pickart, C. M. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair . Cell 96, 645?653 (1999).

    Article  CAS  Google Scholar 

  8. Deng, L. et al. Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain . Cell 103, 351?361 (2000).

    Article  CAS  Google Scholar 

  9. Spence, J. et al. Cell-cycle-regulated modification of the ribosome by a variant multiubiquitin chain. Cell 102, 67? 76 (2000).

    Article  CAS  Google Scholar 

  10. Busch, H. & Goldknopf, I. L. Ubiquitin-protein conjugates . Mol. Cell. Biochem. 40, 173? 187 (1981).

    Article  CAS  Google Scholar 

  11. van Holde, K. E. Chromatin (Springer, New York, 1988).

  12. Spencer, V. A. & Davie, J. R. Role of covalent modifications of histones in regulating gene expression. Gene 240, 1?12 (1999).

    Article  CAS  Google Scholar 

  13. Robzyk, K., Recht, J. & Osley, M. A. Rad6-dependent ubiquitination of histone H2B in yeast . Science 287, 501?504 (2000).Although histones H2A and H2B were known to be monoubiquitylated for more than two decades, this paper provided the first evidence that histone ubiquitylation was important for function. Yeast mutants that cannot ubiquitylate histone H2B grow more slowly than wild-type cells and do not sporulate.

    Article  CAS  Google Scholar 

  14. Pham, A. D. & Sauer, F. Ubiquitin-activating/conjugating activity of TAF(II)250, a mediator of activation of gene expression in Drosophila . Science 289, 2357? 2360 (2000).Drosophila histone H1 is monoubiquitylated by TAF250, an unusual multifunctional protein that seems to carry E1 and E2 activities in the same polypeptide. TAF250 ubiquitylation of H1 seems to be important for the proper regulation of transcriptional activity in Drosophila embryos.

    Article  CAS  Google Scholar 

  15. Jentsch, S., McGrath, J. P. & Varshavsky, A. The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 329, 131? 134 (1987).

    Article  CAS  Google Scholar 

  16. Prakash, L. The structure and function of RAD6 and RAD18 DNA repair genes of Saccharomyces cerevisiae. Genome 31, 597?600 (1989).

    Article  CAS  Google Scholar 

  17. Roest, H. P. et al. Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification . Cell 86, 799?810 (1996).

    Article  CAS  Google Scholar 

  18. Hicke, L. Gettin' down with ubiquitin: turning off cell surface receptors, transporters and channels. Trends Cell Biol. 9, 107? 112 (1999).

    Article  CAS  Google Scholar 

  19. Rotin, D., Staub, O. & Haguenauer-Tsapis, R. Ubiquitination and endocytosis of plasma membrane proteins: Role of Nedd4/Rsp5p family of ubiquitin-protein ligases. J. Membr. Biol. 176, 1?17 ( 2000).

    Article  CAS  Google Scholar 

  20. Strous, G., van Kerkhof, P., Govers, R., Ciechanover, A. & Schwartz, A. L. The ubiquitin conjugation system is required for ligand-induced endocytosis and degradation of the growth hormone receptor. EMBO J. 15, 3806? 3812 (1996).

    Article  CAS  Google Scholar 

  21. Staub, O. et al. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. EMBO J. 16, 6325?6336 (1997).

    Article  CAS  Google Scholar 

  22. Bonifacino, J. S. & Weissman, A. M. Ubiquitin and the control of protein fate in the secretory and endocytic pathways. Annu. Rev. Cell Dev. Biol. 14, 19? 57 (1998).

    Article  CAS  Google Scholar 

  23. Levkowitz, G. et al. c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes Dev. 12, 3663?3674 (1998).

    Article  CAS  Google Scholar 

  24. Lee, P. S. et al. The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation. EMBO J. 18, 3616?3628 ( 1999).

    Article  CAS  Google Scholar 

  25. Levkowitz, G. et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol. Cell 4, 1029?1040 ( 1999).

    Article  CAS  Google Scholar 

  26. Jeffers, M., Taylor, G. A., Weidner, K. M., Omura, S. & Vande Woude, G. F. Degradation of the Met tyrosine kinase receptor by the ubiquitin?proteasome pathway. Mol. Cell. Biol. 17, 799?808 (1997).

    Article  CAS  Google Scholar 

  27. Lucero, P., Penalver, E., Vela, L. & Lagunas, R. Monoubiquitination is sufficient to signal internalization of the maltose transporter in Saccharomyces cerevisiae. J. Bacteriol. 182, 241?243 (2000).

    Article  CAS  Google Scholar 

  28. Nakatsu, F. et al. A di-leucine signal in the ubiquitin moiety: possible involvement in ubiquitin-mediated endocytosis. J. Biol. Chem. 275 , 26213?26219 (2000).

    Article  CAS  Google Scholar 

  29. Roth, A. F. & Davis, N. G. Ubiquitination of the PEST-like endocytosis signal of the yeast a-factor receptor. J. Biol. Chem. 275, 8143?8153 ( 2000).

    Article  CAS  Google Scholar 

  30. Springael, J. Y., Galan, J. M., Haguenauer-Tsapis, R. & André, B. NH4+-induced down-regulation of the Saccharomyces cerevisiae Gap1p permease involves its ubiquitination with lysine-63-linked chains . J. Cell Sci. 112, 1375? 1383 (1999).

    CAS  PubMed  Google Scholar 

  31. Shih, S. C., Sloper-Mould, K. E. & Hicke, L. Monoubiquitin carries a novel internalization signal that is appended to activated receptors. EMBO J. 19 , 187?198 (2000).

    Article  CAS  Google Scholar 

  32. van Delft, S., Govers, R., Strous, G., Verkleij, A. & Van Bergen en Henegouwen, P. Epidermal growth factor induces ubiquitination of Eps15. J. Biol. Chem. 272, 14013? 14016 (1997).

    Article  CAS  Google Scholar 

  33. Wilde, A. et al. EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake. Cell 96, 677?687 ( 1999).

    Article  CAS  Google Scholar 

  34. Fischer-Vize, J. A., Rubin, G. M. & Lehmann, R. The fat facets gene is required for Drosophila eye and embryo development. Development 116, 985?1000 (1992).

    CAS  PubMed  Google Scholar 

  35. Cadavid, A. L., Ginzel, A. & Fischer, J. A. The function of the Drosophila Fat facets deubiquitinating enzyme in limiting photoreceptor cell number is intimately associated with endocytosis. Development 127, 1727?1736 (2000).

    CAS  PubMed  Google Scholar 

  36. Garoff, H., Hewson, R. & Opstelten, D. J. E. Virus maturation by budding. Microbiol. Mol. Biol. Rev. 62, 1171?1190 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Strack, B., Calistri, A., Accola, M. A., Palú, G. & Göttlinger, H. G. A role for ubiquitin ligase recruitment in retrovirus release. Proc. Natl Acad. Sci. USA 97, 13063?13068 ( 2000).This paper shows that ubiquitin is important for virus budding and brings ubiquitin protein ligases into the picture. The proline-rich motifs in viral L domains that mediate interaction with ubiquitin protein ligases are required for Gag ubiquitylation and virus budding.

    Article  CAS  Google Scholar 

  38. Ott, D. E. et al. Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukaemia virus. J. Virol. 72, 2962?2968 ( 1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Patnaik, A., Chau, V. & Wills, J. W. Ubiquitin is part of the retrovirus budding machinery . Proc. Natl Acad. Sci. USA 97, 13069? 13074 (2000).Depletion of intracellular ubiquitin levels inhibits virus budding at a late stage and this defect can be partially restored by fusing ubiquitin in-frame to Gag. This provides evidence that ubiquitylation of Gag is required for release of virus particles from the host cell.

    Article  CAS  Google Scholar 

  40. Schubert, U. et al. Proteasome inhibition interferes with Gag polyprotein processing, release and maturation of human immunodeficiency viruses. Proc. Natl Acad. Sci. USA 97, 13057?13062 (2000).

    Article  CAS  Google Scholar 

  41. Craven, R. C., Harty, R. N., Paragas, J., Palese, P. & Wills, J. W. Late domain function identified in the vesicular stomatitis virus M protein by use of rhabdovirus-retrovirus chimeras. J. Virol. 73, 3359? 3365 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Jayakar, H. R., Murti, K. G. & Whitt, M. A. Mutations in the PPPY motif of vesicular stomatitis virus matrix protein reduce virus budding by inhibiting a late step in virion release. J. Virol. 74, 9818? 9827 (2000).

    Article  CAS  Google Scholar 

  43. Harty, R. N., Brown, M. E., Wang, G., Huibregtse, J. & Hayes, F. P. A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding. Proc. Natl Acad. Sci. USA 97 , 13871?13876 (2000).

    Article  CAS  Google Scholar 

  44. Puffer, B. A., Watkins, S. C. & Montelaro, R. C. Equine infectious anemia virus Gag polyprotein late domain specifically recruits cellular AP-2 adapter protein complexes during virion assembly. J. Virol. 72, 10218? 10221 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Hicke, L. & Riezman, H. Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84, 277?287 ( 1996).

    Article  CAS  Google Scholar 

  46. Galan, J. M., Moreau, V., André, B., Volland, C. & Haguenauer-Tsapis, R. Ubiquitination mediated by the Npi1p/Rsp5p ubiquitin-protein ligase is required for endocytosis of the yeast uracil permease. J. Biol. Chem. 271, 10946?10952 (1996).

    Article  CAS  Google Scholar 

  47. Cook, W., Jeffrey, L., Kasperek, E. & Pickart, C. Structure of tetraubiquitin shows how multiubiquitin chains can be formed . J. Mol. Biol. 236, 601? 609 (1994).

    Article  CAS  Google Scholar 

  48. Beal, R., Deveraux, Q., Xia, G., Rechsteiner, M. & Pickart, C. Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting. Proc. Natl Acad. Sci. USA 93, 861?866 ( 1996).

    Article  CAS  Google Scholar 

  49. Sloper-Mould, K. E., Jemc, J., Pickart, C. M. & Hicke, L. Distinct functional surface regions on ubiquitin (submitted).

  50. Hochstrasser, M. Evolution and function of ubiquitin-like protein-conjugation systems. Nature Cell Biol. 2, E153?E157 (2000).

    Article  CAS  Google Scholar 

  51. Schauber, C. et al. Rad23 links DNA repair to the ubiquitin/proteasome pathway . Nature 391, 715?718 (1998).

    Article  CAS  Google Scholar 

  52. Kleijnen, M. F. et al. The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol. Cell 6, 409?419 (2000).

    Article  CAS  Google Scholar 

  53. Mizushima, N., Noda, T. & Ohsumi, Y. Apg16p is required for the function of the Apg12p?Apg5p conjugate in the yeast autophagy pathway. EMBO J. 18 , 3888?3896 (1999).

    Article  CAS  Google Scholar 

  54. Guarino, L. A., Smith, G. & Dong, W. Ubiquitin is attached to membranes of baculovirus particles by a novel type of phospholipid anchor. Cell 80, 301? 309 (1995).

    Article  CAS  Google Scholar 

  55. Medintz, I., Jiang, H. & Michels, C. A. The role of ubiquitin conjugation in glucose-induced proteolysis of Saccharomyces maltose permease. J. Biol. Chem. 273, 34454?34462 ( 1998).

    Article  CAS  Google Scholar 

  56. Dunn, R. & Hicke, L. Domains of the Rsp5 ubiquitin protein ligase required for receptor-mediated and fluid-phase endocytosis. Mol. Biol. Cell 12, 421?435 (2001).

    Article  CAS  Google Scholar 

  57. Huibregtse, J. M., Yang, J. G. & Beaudenon, S. L. The large subunit of RNA polymerase II is a substrate of the Rsp5 ubiquitin-protein ligase. Proc. Natl Acad. Sci. USA 94, 3656?3661 ( 1997).

    Article  CAS  Google Scholar 

  58. Koegl, M. et al. A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 96, 635? 644 (1999).

    Article  CAS  Google Scholar 

  59. Ortolan, T. G. et al. The DNA repair protein Rad23 is a negative regulator of multi-ubiquitin chain assembly. Nature Cell Biol. 2, 601 ?608 (2000).

    Article  CAS  Google Scholar 

  60. Finley, D., Bartel, B. & Varshavsky, A. The tails of ubiquitin precursors are ribosomal proteins whose fusion to ubiquitin facilitates ribosome biogenesis. Nature 338, 394?401 ( 1989).

    Article  CAS  Google Scholar 

  61. Wolffe, A. Chromatin Structure and Function (Academic, San Diego, 1998).

    Google Scholar 

  62. Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41? 45 (2000).

    Article  CAS  Google Scholar 

  63. Ball, E. et al. Arthrin, a myofibrillar protein of insect flight muscle, is an actin?ubiquitin conjugate. Cell 51, 221?228 (1987).

    Article  CAS  Google Scholar 

  64. Huang, H. et al. The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7 . J. Biol. Chem. 275, 26661? 26664 (2000).

    CAS  Google Scholar 

  65. Arnason, T. & Ellison, M. J. Stress resistance in Saccharomyces cerevisiae is strongly correlated with assembly of a novel type of multiubiquitin chain. Mol. Cell. Biol. 14, 7876? 7883 (1994).

    Article  CAS  Google Scholar 

  66. Baboshina, O. V. & Haas, A. L. Novel multiubiquitin chain linkages catalyzed by the conjugating enzymes E2EPF and RAD6 are recognized by 26S proteasome subunit 5. J. Biol. Chem. 271, 2823?2831 (1996).

    Article  CAS  Google Scholar 

  67. Luger, K., Mader, A. W., Richmond, R. K., Sargent, D. F. & Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389 , 251?260 (1997).

    Article  CAS  Google Scholar 

  68. Joazeiro, C. A. et al. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science 286, 309?312 (1999).

    Article  CAS  Google Scholar 

  69. Staub, O. et al. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. EMBO J. 15, 2371?2380 ( 1996).

    Article  CAS  Google Scholar 

  70. Overton, M. C. & Blumer, K. J. G-protein-coupled receptors function as oligomers in vivo. Curr. Biol. 10, 341?344 (2000).

    Article  CAS  Google Scholar 

  71. Yesilaltay, A. & Jenness, D. D. Homo-oligomeric complexes of the yeast a-factor pheromone receptor are functional units of endocytosis. Mol. Biol. Cell 11, 2873? 2884 (2000).

    Article  CAS  Google Scholar 

  72. Wilkinson, K. D. & Hochstrasser, M. in Ubiquitin and the Biology of the Cell (eds Peters, J. M., Harris, J. R. & Finley, D.) 99?125 (Plenum, New York and London, 1998).

    Book  Google Scholar 

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Acknowledgements

I thank R. Lamb, J. Widom, J. Wills and members of my lab for advice and helpful discussions, and R. Lamb and K. Lee for critical comments on the manuscript. J. Wills, H. Göttlinger, U. Schubert and J. Leis generously communicated unpublished results. I apologize to my colleagues whose work or references were not included owing to space restrictions.

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DATABASE LINKS

H2A

H2B

Rad6

H1

TAF250

Fat facets

epsin

Eps15

growth hormone receptor

Nedd4

AP2

Rpn10

Apg12

SCF ligase

Apg5

Apg8

SUMO-1

Rsp5

Rad23

FURTHER INFORMATION

Structure of monoubiquitin

Hicke lab

ENCYCLOPEDIA OF LIFE SCIENCES

Ubiquitin pathway

Lysosomal degradation of protein

Nucleosomes: detailed structure and mutations

Glossary

HISTONE

A family of small, highly conserved basic proteins, found in the chromatin of all eukaryotic cells, that associate with DNA to form a nucleosome.

ENDOCYTOSIS

Internalization and transport of extracellular material and plasma membrane proteins from the cell surface to intracellular organelles known as endosomes.

RETROVIRUS

RNA virus that uses reverse transcriptase to convert its RNA into DNA.

NUCLEOSOME

The basic structural subunit of chromatin, which consists of 200 base pairs of DNA and an octamer of histones.

SPORULATION

Sexual reproduction in yeast and fungi.

UBIQUITIN-CONJUGATING ENZYME (E2)

An enzyme that accepts ubiquitin from a ubiquitin-activating enzyme (E1) and, together with a ubiquitin ligase (E3), transfers it to a substrate protein.

TAF250

A subunit of TFIID, where TAF stands for TBP-associated factor, and TBP stands for TATA-box-binding protein.

TFIID

Transcription factor IID. A multisubunit general transcription factor, necessary for the transcription of all genes in eukaryotes.

LYSOSOME

A membrane-bounded organelle with a low internal pH (4?5) that contains hydrolytic enzymes and that is the site of the degradation of proteins in both the biosynthetic and the endocytic pathways.

EPS15

Epidermal growth factor receptor pathway substrate clone 15. Mammalian protein required for budding of clathrin-coated vesicles during endocytosis.

CLATHRIN

The main component of the coat that is associated with clathrin-coated vesicles, which are involved in membrane transport both in the endocytic and biosynthetic pathways.

DE-UBIQUITYLATING ENZYME

Enzyme that catalyses the cleavage of ubiquitin from multi-ubiquitin chains or protein conjugates.

GROWTH HORMONE RECEPTOR

A signal transducing receptor of the tyrosine-kinase family.

GAG

The protein of the nucleocapsid shell around the RNA of a retrovirus.

POLYPROTEIN

A single polypeptide chain that is cleaved into several separate proteins.

UBIQUITIN PROTEIN LIGASE (E3)

An enzyme that acts together with a ubiquitin-conjugating enzyme (E2) to couple the small protein ubiquitin to lysine residues on a target protein, marking that protein for destruction by the proteasome.

SCANNING ALANINE MUTAGENESIS

A method for determining the function of every residue in a protein sequence by mutating each one to alanine.

CULLIN

A family of proteins present in multisubunit ubiquitin ligases; they recruit RING-finger-containing proteins to the ligase complex.

SCF UBIQUITIN LIGASE

A multisubunit ubiquitin ligase that contains Skp1, a member of the cullin family (Cul1), and an F-box-containing protein (Skp2), as well as a RING-finger-containing protein (Roc1/Rbx1).

GATE-16

Protein with a ubiquitin fold, required for intra-Golgi transport and autophagy.

CHAPERONE

A protein that ensures the proper folding of other proteins.

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Hicke, L. Protein regulation by monoubiquitin . Nat Rev Mol Cell Biol 2, 195–201 (2001). https://doi.org/10.1038/35056583

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