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Gene Review

ubl-1  -  Protein UBL-1

Caenorhabditis elegans

 
 
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High impact information on ubiquitin

  • Loss of function in the C. elegans rpm-1 gene, a putative RING finger/E3 ubiquitin ligase, causes disorganized presynaptic cytoarchitecture [1].
  • Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development [1].
  • Here we show that the CUL-4 ubiquitin ligase temporally restricts DNA-replication licensing in Caenorhabditis elegans [2].
  • Here we show that LIN-23, the substrate binding subunit of a Skp1/Cullin/F Box (SCF) ubiquitin ligase, regulates the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of C. elegans [3].
  • 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 [4].
 

Biological context of ubiquitin

  • 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].
  • 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 [6].
  • We show that inactivation of CUL-2, a member of the cullin family of ubiquitin ligases, delays or abolishes meiotic anaphase II with no effect on anaphase I, indicating differential regulation during the two meiotic stages [7].
  • We present the first crystal structure of a NAC protein revealing two structural features: (i) a novel unique protein fold that mediates dimerization of the complex, and (ii) a ubiquitin-associated domain that suggests a yet unidentified role for NAC in the cellular protein quality control system via the ubiquitination pathway [8].
  • This mutant is allelic to lin-23, which codes for an F-box-containing component of an SCF E3 ubiquitin ligase complex that was previously shown to negatively regulate postembryonic cell divisions [9].
 

Anatomical context of ubiquitin

  • 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 [10].
  • 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 [10].
  • A genetic screen for neurite outgrowth mutants in Caenorhabditis elegans reveals a new function for the F-box ubiquitin ligase component LIN-23 [9].
  • CONCLUSIONS: Since it is known that the MTOC in the fertilized embryo is contributed by sperm asters in C. elegans, we suggest that UCH/CeUBP130 and ubiquitin protein degradation pathways may be involved in microtubule-based sperm aster formation [11].
  • The ubiquitin-protein conjugation system is involved in a variety of eukaryotic cell functions, including the degradation of abnormal and short-lived proteins, chromatin structure, cell cycle progression, and DNA repair [12].
 

Associations of ubiquitin with chemical compounds

  • The crystal structure of archaeal nascent polypeptide-associated complex (NAC) reveals a unique fold and the presence of a ubiquitin-associated domain [8].
 

Other interactions of ubiquitin

  • The Caenorhabditis elegans sel-10 protein is structurally similar to E3 ubiquitin ligases and is a negative regulator of Notch (lin-12) and presenilin signaling [13].
  • The cyk-3 gene has been identified and found to encode a ubiquitin C-terminal hydrolase that is active against model substrates [14].
  • Caenorhabditis elegans gene ubc-25 encodes a novel type of an E2 ubiquitin transferase domain (UBCc) protein, which is highly conserved in multicellular animals, but which is not present in the genomes of fungi or plants [15].
  • A ubiquitin C-terminal hydrolase is required to maintain osmotic balance and execute actin-dependent processes in the early C. elegans embryo [14].
  • OMA-1 proteolysis also depends on Cyclin B3 and on a ZIF-1-independent CUL-2-based E3 ubiquitin ligase complex, as well as the CUL-2-interacting protein ZYG-11 and the Skp1-related proteins SKR-1 and SKR-2 [16].
 

Analytical, diagnostic and therapeutic context of ubiquitin

  • A recently identified molecule C-terminus of Hsc70 interacting protein (CHIP) has been reported to be an E3 ubiquitin ligase collaborating with molecular chaperones for the degradation of misfolded or unfolded proteins [17].
  • Ubiquitin siRNA or dsRNA delivered by soaking or electroporation inhibited development in T. colubriformis but with feeding as a delivery method, RNAi of ubiquitin was not successful [18].

References

  1. Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development. Nakata, K., Abrams, B., Grill, B., Goncharov, A., Huang, X., Chisholm, A.D., Jin, Y. Cell (2005) [Pubmed]
  2. CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Zhong, W., Feng, H., Santiago, F.E., Kipreos, E.T. Nature (2003) [Pubmed]
  3. LIN-23-mediated degradation of beta-catenin regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of C. elegans. Dreier, L., Burbea, M., Kaplan, J.M. Neuron (2005) [Pubmed]
  4. 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]
  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. 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]
  7. CUL-2 and ZYG-11 promote meiotic anaphase II and the proper placement of the anterior-posterior axis in C. elegans. Liu, J., Vasudevan, S., Kipreos, E.T. Development (2004) [Pubmed]
  8. The crystal structure of archaeal nascent polypeptide-associated complex (NAC) reveals a unique fold and the presence of a ubiquitin-associated domain. Spreter, T., Pech, M., Beatrix, B. J. Biol. Chem. (2005) [Pubmed]
  9. A genetic screen for neurite outgrowth mutants in Caenorhabditis elegans reveals a new function for the F-box ubiquitin ligase component LIN-23. Mehta, N., Loria, P.M., Hobert, O. Genetics (2004) [Pubmed]
  10. 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]
  11. A deubiquitinating enzyme, UCH/CeUBP130, has an essential role in the formation of a functional microtubule-organizing centre (MTOC) during early cleavage in C. elegans. Lee, J., Jee, C., Lee, J.I., Lee, M.H., Lee, M.H., Koo, H.S., Chung, C.H., Ahnn, J. Genes Cells (2001) [Pubmed]
  12. The ubc-2 gene of Caenorhabditis elegans encodes a ubiquitin-conjugating enzyme involved in selective protein degradation. Zhen, M., Heinlein, R., Jones, D., Jentsch, S., Candido, E.P. Mol. Cell. Biol. (1993) [Pubmed]
  13. The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog. Oberg, C., Li, J., Pauley, A., Wolf, E., Gurney, M., Lendahl, U. J. Biol. Chem. (2001) [Pubmed]
  14. A ubiquitin C-terminal hydrolase is required to maintain osmotic balance and execute actin-dependent processes in the early C. elegans embryo. Kaitna, S., Schnabel, H., Schnabel, R., Hyman, A.A., Glotzer, M. J. Cell. Sci. (2002) [Pubmed]
  15. The maintenance of neuromuscular function requires UBC-25 in Caenorhabditis elegans. Schulze, E., Altmann, M.E., Adham, I.M., Schulze, B., Fröde, S., Engel, W. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  16. The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans. Shirayama, M., Soto, M.C., Ishidate, T., Kim, S., Nakamura, K., Bei, Y., van den Heuvel, S., Mello, C.C. Curr. Biol. (2006) [Pubmed]
  17. Molecular and functional analysis of Caenorhabditis elegans CHIP, a homologue of Mammalian CHIP. Khan, L.A., Nukina, N. FEBS Lett. (2004) [Pubmed]
  18. Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. Issa, Z., Grant, W.N., Stasiuk, S., Shoemaker, C.B. Int. J. Parasitol. (2005) [Pubmed]
 
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