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