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Gene Review

ned-8  -  Protein NED-8

Caenorhabditis elegans

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Disease relevance of ubiquitin


High impact information on ubiquitin

  • Indeed, we identify a unique amino acid substitution in the P loop motif (K454A) that uncouples nucleolar localization and E3 ubiquitin ligase activity of Mdm2 and leads to upregulation of the E3 activity both in human cells and in Caenorhabditis elegans [2].
  • Furthermore, we demonstrate that the DNA damage checkpoint promotes the association between BRCA1 and UbcH5c to form an active E3-Ub ligase on chromatin after IR [3].
  • Neuronal CIP4 immunoreactivity increased with neuropathological severity in the neostriatum of HD patients and partially colocalized to ubiquitin-positive aggregates [4].
  • We propose that the CUL-4/DDB-1 ubiquitin ligase is the principal E3 for regulating the extent of DNA replication in C. elegans [5].
  • Genetic screens in Caenorhabditis elegans and Drosophila have implicated signaling pathways that may involve small G-proteins, ubiquitin-mediated protein degradation and selective cell adhesion in target recognition, synaptic assembly and growth [6].

Biological context of ubiquitin

  • The Nedd8 ubiquitin-like protein modification pathway regulates cell-cycle progression [7].
  • We propose that Nedd8-modified cullin, as part of an E3 ubiquitin ligase complex, targets katanin for degradation during the transition from meiosis to mitosis [7].
  • The progeny of both ned-8 and ubc-12 RNAi-treated hermaphrodites either arrested during embryonic development or underwent abnormal postembryonic development [8].
  • Based on genetic studies, HIW has been implicated in ubiquitination, possibly functioning as an E3 ubiquitin ligase through the RING zinc finger domain [9].
  • Here we report the NMR structure of the N-terminal domain of Caenorhabditis elegans CoB and show that it closely resembles ubiquitin as was recently postulated on the basis of bioinformatic analysis (Grynberg, M., Jaroszewski, L., and Godzik, A. (2003) BMC Bioinformatics 4, 46) [10].

Anatomical context of ubiquitin

  • The degradation of proteins through ubiquitin-mediated proteolysis has been previously shown to regulate the cell cycle and AP axis formation in the C. elegans zygote [11].
  • It has been reported that the AAA ATPase p97/VCP/CDC48 is required in this pathway for protein dislocation across the ER membrane and subsequent ubiquitin dependent degradation by the 26S proteasome in the cytosol [12].
  • Protein degradation mediated by the ubiquitin/proteasome system is *essential for the elimination of misfolded proteins from the endoplasmic reticulum (ER) to adapt to ER stress [12].
  • MAFbx/Atrogin-1 has been identified as a regulator for skeletal muscle atrophy and encodes an F-box-type E3 ubiquitin ligase [13].

Associations of ubiquitin with chemical compounds


Physical interactions of ubiquitin

  • Thus, the RBX1/CUL2/ELC1/ELB1 complex acts as an E3 ubiquitin ligase in C. elegans and is essential for diverse functions relevant to chromosomal dynamics and cell cycle control [15].

Other interactions of ubiquitin

  • Additionally, both ned-8 and ubc-12 RNAi induced a striking abnormality in the alae, structures produced by the lateral hypodermal seam cells in the adult nematode [8].
  • Apart from the new HEAT and Armadillo domains in cofactor D and an unusual spectrin-like domain in cofactor C, we have identified a new subfamily of ubiquitin-like domains in cofactors B and E. Together, these observations provide a reliable, molecular level model of cofactor complex [16].
  • The anaphase-promoting complex/cyclosome (APC/C) is one of two key E3 ubiquitin ligase complexes that functions in regulating cell cycle transitions in proliferating cells by acting on cyclins and components of the mitotic/meiotic apparatus [17].


  1. A Caenorhabditis elegans Parkin mutant with altered solubility couples alpha-synuclein aggregation to proteotoxic stress. Springer, W., Hoppe, T., Schmidt, E., Baumeister, R. Hum. Mol. Genet. (2005) [Pubmed]
  2. Nucleotide binding by the Mdm2 RING domain facilitates Arf-independent Mdm2 nucleolar localization. Poyurovsky, M.V., Jacq, X., Ma, C., Karni-Schmidt, O., Parker, P.J., Chalfie, M., Manley, J.L., Prives, C. Mol. Cell (2003) [Pubmed]
  3. A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage sites. Polanowska, J., Martin, J.S., Garcia-Muse, T., Petalcorin, M.I., Boulton, S.J. EMBO J. (2006) [Pubmed]
  4. Cdc42-interacting protein 4 binds to huntingtin: neuropathologic and biological evidence for a role in Huntington's disease. Holbert, S., Dedeoglu, A., Humbert, S., Saudou, F., Ferrante, R.J., Néri, C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. The Caenorhabditis elegans Replication Licensing Factor CDT-1 Is Targeted for Degradation by the CUL-4/DDB-1 Complex. Kim, Y., Kipreos, E.T. Mol. Cell. Biol. (2007) [Pubmed]
  6. Synaptogenesis: insights from worm and fly. Jin, Y. Curr. Opin. Neurobiol. (2002) [Pubmed]
  7. Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway. Kurz, T., Pintard, L., Willis, J.H., Hamill, D.R., Gönczy, P., Peter, M., Bowerman, B. Science (2002) [Pubmed]
  8. The NED-8 conjugating system in Caenorhabditis elegans is required for embryogenesis and terminal differentiation of the hypodermis. Jones, D., Candido, E.P. Dev. Biol. (2000) [Pubmed]
  9. Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex. Murthy, V., Han, S., Beauchamp, R.L., Smith, N., Haddad, L.A., Ito, N., Ramesh, V. J. Biol. Chem. (2004) [Pubmed]
  10. Solution structure of a ubiquitin-like domain from tubulin-binding cofactor B. Lytle, B.L., Peterson, F.C., Qiu, S.H., Luo, M., Zhao, Q., Markley, J.L., Volkman, B.F. J. Biol. Chem. (2004) [Pubmed]
  11. The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit and anteroposterior polarity in the one-cell Caenorhabditis elegans embryo. Lyczak, R., Zweier, L., Group, T., Murrow, M.A., Snyder, C., Kulovitz, L., Beatty, A., Smith, K., Bowerman, B. Development (2006) [Pubmed]
  12. A conserved role of Caenorhabditis elegans CDC-48 in ER-associated protein degradation. Mouysset, J., K??hler, C., Hoppe, T. J. Struct. Biol. (2006) [Pubmed]
  13. MFB-1, an F-box-type ubiquitin ligase, regulates TGF-beta signalling. Aoyama, Y., Urushiyama, S., Yamada, M., Kato, C., Ide, H., Higuchi, S., Akiyama, T., Shibuya, H. Genes Cells (2004) [Pubmed]
  14. The anaphase-promoting complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of C. elegans. Juo, P., Kaplan, J.M. Curr. Biol. (2004) [Pubmed]
  15. Caenorhabditis elegans Elongin BC complex is essential for cell proliferation and chromosome condensation and segregation during mitosis and meiotic division II. Sasagawa, Y., Kikuchi, K., Dazai, K., Higashitani, A. Chromosome Res. (2005) [Pubmed]
  16. Domain analysis of the tubulin cofactor system: a model for tubulin folding and dimerization. Grynberg, M., Jaroszewski, L., Godzik, A. BMC Bioinformatics (2003) [Pubmed]
  17. APC/C regulation of axonal growth and synaptic functions in postmitotic neurons: the Liprin-alpha connection. Teng, F.Y., Tang, B.L. Cell. Mol. Life Sci. (2005) [Pubmed]
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