COPS6

..However, the mechanistic regulation of each subunit in cancer remains unclear. Among the CSN subunits, CSN5 and CSN6 are the only two that each contain an MPN (Mpr1p and Pad1p N-terminal) domain...

..Moreover, we observed that activation of the Nod1 apoptotic pathway leads to specific cleavage of the subunit CSN6. This cleavage is concomitant with caspase processing and generates a short amino-terminal peptide of 3 kDa...

..Among its eight subunits, CSN5 and CSN6 contain a characteristic MPN (for Mpr1p and Pad1p N-terminal) domain and, in Arabidopsis thaliana, are each encoded ..

..Our data suggest that enhancement of CSN-mediated deneddylation by CAND1 may contribute to its function as a positive regulator of SCFs in vivo...

..Further, we also discuss caveats and future directions for investigation of the interesting biology of this HIV accessory gene...

..Finally, endogenous CoIP of MIF-CSN6 complexes from mammalian cells demonstrated that MPN is responsible for MIF-JAB1 binding in vivo, and, as CSN6 does ..

..b>CSN6 haploinsufficiency restored growth, whereas reduction of proteasome subunits RPN8 or RPN11 had no effect...

..This apparent paradox can be resolved in a model that proposes CSN-mediated cullin inhibition is a prerequisite for the proper assembly and maintenance of active cullin ubiquitin ligase complexes...

..Knockdown of CSN with RNA interference leads to defects in NER. These results suggest that the distinct UV response of the DDB2 and CSA complexes is involved in diverse mechanisms of NER...

..This finding and amino acid sequence comparisons can explain why the MPN-containing proteins Mov34/PSMD7, RPN8, Csn6, Prp8p and the translation initiation factor 3 subunits f and h do not show catalytic isopeptidase activity, ..

..However, little is known about the CSN during apoptosis. We demonstrate in vitro and in vivo that CSN6 is cleaved most effectively by caspase 3 at D23 after 2-3 h of apoptosis induced by anti-Fas-Ab or etoposide...

..we show that a C-terminal tail outside of this PCI domain is responsible for association with the non-PCI subunit, CSN6. In vivo studies of transgenic plants revealed that the overexpressed CSN7 PCI domain does not assemble into the ..

..We show for the first time that COP9 signalosome subunit 6 (CSN6) associates with COP1 and is involved in 14-3-3? ubiquitin-mediated degradation...

Zebrafish cops6 encodes a putative deubiquitylating enzyme (DUB) that belongs to the JAMM family. It consists of 297 amino acids and includes the Mov34/MPN/PAD-1 (PF01398) domain...

..Its role in tumor development, however, remains unclear. Here, we have shown that the COP9 subunit 6 (CSN6) gene is amplified in human breast cancer specimens, and the CSN6 protein is upregulated in human breast and ..

..We compare the structure of CSN with its homologous complexes, the 26S proteasome lid and eIF3, and propose a conserved architecture implying similar assembly pathways and/or conserved substrate interaction modes...

..We showed that ELIP, CSN6, SOS2 and RBP are related to the photocontrol of germination...

..network of the mammalian CSN through mass spectrometric interrogation of the CSN subunits Csn1, Csn3, Csn4, Csn5, Csn6 and Csn7a...

..criterion, 11 genes were selected: ELF3 and SLC45A3 on 1q; CLDN12, CDK6, SMURF1, ARPC1B, ZKSCAN1, MCM7, and COPS6 on 7q; and FDFT1 and CTSB on 8p...

..map that shows two symmetrical modules, Csn1/2/3/8 and Csn4/5/6/7, connected by interactions between Csn1-Csn6. Overall the stable modules and multiple subcomplexes observed here are in agreement with the "mini-CSN" ..

..Curcumin treatment results in elevated amounts of c-Jun-Ub conjugates. We conclude that CK2 and PKD are recruited by CSN in order to regulate Ub conjugate formation...

..Comparative analyses of the subunit interaction of CSN revealed a set of conserved subunit contacts and resulted in a model of CSN subunit topology, some aspects of which were substantiated by in vivo cross-link tests...

..We have cloned a candidate Vpr ligand, termed human Vpr interacting protein (hVIP/MOV34), by using a yeast two-hybrid assay...

..The subunit composition of eIF3 appears to be highly conserved in Drosophila melanogaster, C. elegans, and Arabidopsis thaliana, whereas only 5 homologs of the 10 subunits of mammalian eIF3 are encoded in S. cerevisiae...

..These results are consistent with the hypothesis that Vpr induces G2 arrest through pathways that are similar to those utilized by DNA-damaging agents...

..These results suggest that RIP may be involved in Vpr function...

..Cell cycle arrest induced by Vpr correlates with an increase in the hyperphosphorylated (inactive) form of the cyclin-dependent serine/threonine kinase CDC2, consistent with an arrest of cells at the boundary of G2 and M...

..We speculate that Vpr has two sites for interaction with cellular factors: one in the alpha-helical region that specifies nuclear localization and one in the carboxy-terminal domain that is required for Cdc2 inhibition...

..These studies demonstrate that HIV-1 vpr has profound effects on the cellular factors which control entry into mitosis and indicate vpr's potential contribution to the cellular pathology associated with HIV-1 infection...

..In vivo, Vpr might, by preventing p34cdc2 activation, delay or prevent apoptosis of infected cells. This would increase the amount of virus each infected cell produced...

..Three subunits of the new complex--Sgn3, Sgn5/JAB1, and Sgn6--exhibit sequence similarities to regulatory components of the 26S proteasome, which could indicate the existence ..

..Our data suggest that Vpr mediates G(2) arrest by enhancing the nuclear import of PP2A and by positively modulating its catalytic activity towards active phosphorylated nuclear cdc25...

..This conclusion was further supported by the observation that mutations in Vpr, which have lost their ability to induce G2 arrest, retained the ability to kill cells...

..Stable expression of CDK11(p46) in vivo inhibited the synthesis of a transfected luciferase reporter protein and overall cellular protein synthesis. These data provide insight into the cellular function of CDK11 during apoptosis...

..hVIP/mov34 (human Vpr Interacting Protein) is one of these identified Vpr ligands...

..with Int-6 as bait, we have isolated subunits belonging to all three complexes, namely eIF3-p110, Rpt4, CSN3 and CSN6. The results of transient expression experiments in COS7 cells confirmed the interaction of Int-6 with Rpt4, CSN3 ..

..The CSN6 proteins share homology with CSN5 and belong to the Mov34 superfamily of proteins...

....

..It induces the cyclin-dependent inhibitor p21. In HeLa and MCF-7 cells, inhibition of CSN kinase by curcumin or Deltap53(145-164) results in accumulation of endogenous p53...

..In this report, we demonstrate that the mere expression of a cellular protein, hVIP/mov34, which we earlier identified as a cellular HIV-1 Vpr ligand, in two different vectors clearly altered its ..

..We expect that these studies will greatly enrich our understanding of HER2-mediated p27 degradation in cancer and will help develop p27 as a novel therapeutic agent for HER2-associated cancers. ..

..to elucidate the molecular mechanism of mammalian constitutive photomorphogenesis 9 signalosome (COP9) subunit 6 (CSN6)-mediated p27 degradation and to illustrate it as a signal target of HER2/Akt signals involved in degrading p27...