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E2-c-Cbl recognition is necessary but not sufficient for ubiquitination activity.

Huang A, de Jong RN, Wienk H, Winkler GS, Timmers HT, Boelens R
J Mol Biol 385 507-19 (2009)
Cited: 26 times
EuropePMC logo PMID: 18996392

Abstract

The E2 ubiquitin-conjugating enzymes UbcH7 and UbcH5B both show specific binding to the RING (really interesting new gene) domain of the E3 ubiquitin-protein ligase c-Cbl, but UbcH7 hardly supports ubiquitination of c-Cbl and substrate in a reconstituted system. Here, we found that neither structural changes nor subtle differences in the E2-E3 interaction surface are possible explanations for the functional specificity of UbcH5B and UbcH7 in their interaction with c-Cbl. The quick transfer of ubiquitin from the UbcH5B-Ub thioester to c-Cbl or other ubiquitin acceptors suggests that UbcH5B might functionally be a relatively pliable E2 enzyme. In contrast, the UbcH7-Ub thioester is too stable to transfer ubiquitin under our assay conditions, indicating that UbcH7 might be a more specific E2 enzyme. Our results imply that the interaction specificity between c-Cbl and E2 is required but not sufficient for transfer of ubiquitin to potential targets.

Reviews citing this publication (7)

  1. RING domain E3 ubiquitin ligases. Deshaies RJ, Joazeiro CA. Annu Rev Biochem 78 399-434 (2009)
  2. Ubiquitin Ligases: Structure, Function, and Regulation. Zheng N, Shabek N. Annu Rev Biochem 86 129-157 (2017)
  3. Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Bedford L, Lowe J, Dick LR, Mayer RJ, Brownell JE. Nat Rev Drug Discov 10 29-46 (2011)
  4. The role of ubiquitination in tumorigenesis and targeted drug discovery. Deng L, Meng T, Chen L, Wei W, Wang P. Signal Transduct Target Ther 5 11 (2020)
  5. Macromolecular juggling by ubiquitylation enzymes. Lorenz S, Cantor AJ, Rape M, Kuriyan J. BMC Biol 11 65 (2013)
  6. Structural basis of generic versus specific E2-RING E3 interactions in protein ubiquitination. Gundogdu M, Walden H. Protein Sci 28 1758-1770 (2019)
  7. Cbl-family proteins as regulators of cytoskeleton-dependent phenomena. Lee H, Tsygankov AY. J Cell Physiol 228 2285-2293 (2013)

Articles citing this publication (19)

  1. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. Nature 474 105-108 (2011)
  2. Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin ligase complex. Bentley ML, Corn JE, Dong KC, Phung Q, Cheung TK, Cochran AG. EMBO J 30 3285-3297 (2011)
  3. Ubiquitin in motion: structural studies of the ubiquitin-conjugating enzyme∼ubiquitin conjugate. Pruneda JN, Stoll KE, Bolton LJ, Brzovic PS, Klevit RE. Biochemistry 50 1624-1633 (2011)
  4. Smac mimetics activate the E3 ligase activity of cIAP1 protein by promoting RING domain dimerization. Feltham R, Bettjeman B, Budhidarmo R, Mace PD, Shirley S, Condon SM, Chunduru SK, McKinlay MA, Vaux DL, Silke J, Day CL. J Biol Chem 286 17015-17028 (2011)
  5. Contribution of E3-ubiquitin ligase activity to HIV-1 restriction by TRIM5alpha(rh): structure of the RING domain of TRIM5alpha. Lienlaf M, Hayashi F, Di Nunzio F, Tochio N, Kigawa T, Yokoyama S, Diaz-Griffero F. J Virol 85 8725-8737 (2011)
  6. RING domain dimerization is essential for RNF4 function. Liew CW, Sun H, Hunter T, Day CL. Biochem J 431 23-29 (2010)
  7. Autoinhibition and phosphorylation-induced activation mechanisms of human cancer and autoimmune disease-related E3 protein Cbl-b. Kobashigawa Y, Tomitaka A, Kumeta H, Noda NN, Yamaguchi M, Inagaki F. Proc Natl Acad Sci U S A 108 20579-20584 (2011)
  8. The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor. Zhang L, Fairall L, Goult BT, Calkin AC, Hong C, Millard CJ, Tontonoz P, Schwabe JW. Genes Dev 25 1262-1274 (2011)
  9. Anti-Ro52 autoantibodies from patients with Sjögren's syndrome inhibit the Ro52 E3 ligase activity by blocking the E3/E2 interface. Espinosa A, Hennig J, Ambrosi A, Anandapadmanaban M, Abelius MS, Sheng Y, Nyberg F, Arrowsmith CH, Sunnerhagen M, Wahren-Herlenius M. J Biol Chem 286 36478-36491 (2011)
  10. Regulation of ubiquitin transfer by XIAP, a dimeric RING E3 ligase. Nakatani Y, Kleffmann T, Linke K, Condon SM, Hinds MG, Day CL. Biochem J 450 629-638 (2013)
  11. E2 conjugating enzyme selectivity and requirements for function of the E3 ubiquitin ligase CHIP. Soss SE, Yue Y, Dhe-Paganon S, Chazin WJ. J Biol Chem 286 21277-21286 (2011)
  12. Selective recruitment of an E2~ubiquitin complex by an E3 ubiquitin ligase. Spratt DE, Wu K, Kovacev J, Pan ZQ, Shaw GS. J Biol Chem 287 17374-17385 (2012)
  13. NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase. Chasapis CT, Kandias NG, Episkopou V, Bentrop D, Spyroulias GA. Proteins 80 1484-1489 (2012)
  14. A strong 13C chemical shift signature provides the coordination mode of histidines in zinc-binding proteins. Barraud P, Schubert M, Allain FH. J Biomol NMR 53 93-101 (2012)
  15. Balancing Protein Stability and Activity in Cancer: A New Approach for Identifying Driver Mutations Affecting CBL Ubiquitin Ligase Activation. Li M, Kales SC, Ma K, Shoemaker BA, Crespo-Barreto J, Cangelosi AL, Lipkowitz S, Panchenko AR. Cancer Res 76 561-571 (2016)
  16. Cbl interacts with multiple E2s in vitro and in cells. Liyasova MS, Ma K, Voeller D, Ryan PE, Chen J, Klevit RE, Lipkowitz S. PLoS One 14 e0216967 (2019)
  17. NMR characterization of foldedness for the production of E3 RING domains. Huang A, de Jong RN, Folkers GE, Boelens R. J Struct Biol 172 120-127 (2010)
  18. In Vitro Ubiquitination Platform Identifies Methyl Ellipticiniums as Ubiquitin Ligase Inhibitors. Wilson BAP, Voeller D, Smith EA, Wamiru A, Goncharova EI, Liu G, Lipkowitz S, O'Keefe BR. SLAS Discov 26 870-884 (2021)
  19. Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance. Wu M, Sun L, Pessetto ZY, Zang Z, Xie X, Zhong L, Su Q, Zan W, Gao X, Zhao Y, Sun Y. PLoS One 10 e0135916 (2015)


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