Disease relevance of RBX1

• The cells used in this study were ROC-1 oligodendroglia, N1E-115 neuroblastoma, and human umbilical vein endothelial (HUVE) cells [1].

High impact information on RBX1

• Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1 [2].
• Cand1, a 120 kDa HEAT repeat protein, forms a tight complex with the Cul1-Roc1 SCF catalytic core, inhibiting the assembly of the multisubunit E3 complex [3].
• Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity [4].
• ROC1 plays a unique role in the ubiquitination reaction by heterodimerizing with cullin 1 to catalyze ubiquitin polymerization [5].
• CUL7 is a large polypeptide containing a cullin domain, which is responsible for ROC1 binding, and a DOC domain, which is also present in the anaphase-promoting complex [6].

Biological context of RBX1

• Furthermore, endogenous levels of pro-caspase-3 were decreased by overexpression of SAG/ROC-SCF(beta-TrCP) E3 Ub ligases, but increased on siRNA silencing of SAG, regulator of cullin-1 (ROC1), or beta-TrCPs, leading to increased apoptosis by etoposide and TNF-related apoptosis-inducing ligand through increased activation of caspase-3 [7].
• The SCF-ROC1 ubiquitin-protein isopeptide ligase (E3) ubiquitin ligase complex targets the ubiquitination and subsequent degradation of protein substrates required for the regulation of cell cycle progression and signal transduction pathways [8].
• The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is essential to rescue the E3 ligase Rbx1 [9].

Anatomical context of RBX1

• Here we show that in primary human T lymphocytes, the SCF(skp2) core components Roc1, Cul1 and Skp1 are constitutively expressed, and their levels remain unchanged upon TCR/CD3-plus-CD28 costimulation [10].

Associations of RBX1 with chemical compounds

• The cDNA codes for a 21-kDa protein, salmon hyperosmotic protein 21 (Shop21), with 98% identity to Rbx1, an E3 ubiquitin ligase; the protein also contains a novel 81-amino acid domain at the NH(2) terminus not found in Rbx1 [11].

Physical interactions of RBX1

• Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins [12].

Regulatory relationships of RBX1

• Replacement of each of the six residues with the corresponding amino acid in ubiquitin decreases the ability of Nedd8 to activate the ubiquitin ligase activity of ROC1-CUL1 [13].

Other interactions of RBX1

• RING finger mutations of ROC1 eliminated the Ub ligase activity toward cyclin D1 [14].
• An E3 ubiquitin ligase complex ROC1-SCF(Fbw1a) consisting of ROC1, Skp1, Cullin1, and Fbw1a (also termed betaTrCP1) induces ubiquitination of Smad3 [12].
• Smad3 interacts with a RING finger protein, ROC1, through its C-terminal MH2 domain in a ligand-dependent manner [12].
• In productively infected cells, E1B-55K and E4orf6 assemble a ubiquitin ligase with cellular proteins Elongins B and C, Cullin 5 and RBX1 that polyubiquitinates p53 and one or more subunits of the MRN complex involved in DNA double-strand break repair, directing them to proteosomal degradation [15].
• No coding region sequence variations were detected for the elongin B, elongin C or Rbx1 genes [16].

References