Disease relevance of COPS2

• ECG of the month. Alien intruders. Ventricular parasystole [1].

High impact information on COPS2

• Pcu4, Csn1, and Csn2 promote the degradation of Spd1, identifying a new function for the signalosome as a regulator of Pcu4-containing E3 ubiquitin ligase [2].
• CK2 phosphorylates CSN2 and CSN7, and PKD modifies CSN7 [3].
• In both cases the Alien Antigens are also artefacts, resulting from genetic heterogeneity in either mice or cell lines [4].
• It is also unlikely that the successive experimental plagues that created the Alien Antigens are unique to this corner of tumour immunology [4].
• Functional assays indicated that Alien, but not NCoR, displays selectivity for different VDRE structures for transferring these repressive effects into gene regulatory activities [5].

Biological context of COPS2

• However, it inhibits c-Jun and CSN2 phosphorylation by the isolated CSN complex and by the recombinant CK2 [6].
• DNA from one of the CSN/BAC clones was used as a probe for in situ hybridization to show that the CSN1 and CSN2 gene cluster is located on chromosome 15 band q23 and not on chromosome 12 as had been previously reported [7].
• Here, we show that Alien and Sin3A reside together in vivo with the vitamin D3 receptor on the human 24-hydroxylase (CYP24) promoter containing vitamin D3 response elements by chromatin immunoprecipitation [8].
• PCR on the bell pepper genomic DNA using the Alien TIR consensus sequence as primer yielded DNA fragments of nearly 400 bp [9].
• Interestingly, the TIR of the Alien elements shares high homology with sequences existing in the TIR of extrachromosomal linear pSKL DNA plasmid of Saccharomyces kluyveri [10].

Anatomical context of COPS2

• The Drosophila alien gene is highly homologous to the human thyroid receptor interacting protein, TRIP15/COPS2, which is a component of the recently identified signalosome protein complex [11].
• Furthermore, Northern experiments demonstrate that Alien is expressed in the adrenal gland and testis in tissues where DAX-1 is specifically expressed [12].
• However, it has been shown that the CSN2 gene, and this gene only, can be induced in certain mammary cell lines, such as HC11 [7].

Associations of COPS2 with chemical compounds

• We have previously characterized a novel corepressor, termed Alien, which interacts with TR and the ecdysone receptor but not with the retinoic acid receptors RAR or RXR [12].
• Functional analyses revealed that Alien, DAX-1 and thyroid hormone receptor mediated transcriptional silencing is strongly enhanced in the presence of active MLK2 [13].
• Moreover, superrepression via Alien was found to be affected only in part by HDAC inhibitors such as trichostatin A [5].
• In this study, we report the relationship between uric acid and various cardiovascular risk factors in 1,027 healthy Taiwanese adults living in Alien, an agricultural town in subtropical South Taiwan. Serum uric acid levels increased in proportion to age in women, but not in men [14].

Physical interactions of COPS2

• Naturally occurring mutants of the DAX-1 gene fail to interact with Alien and have lost silencing function [12].
• Here, we isolated the mixed lineage kinase 2 (MLK2) as an interacting partner for the corepressor Alien using a yeast two hybrid screen [13].

Other interactions of COPS2

• The c-Jun activation caused by Sgn2 overexpression is independent of JNK and mitogen-activated protein kinase kinase 4 [15].
• Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenita [12].
• Functionally, co-expression of Sin3A enhances Alien-mediated gene repression and overexpression of the HCR alone leads to the inhibition of Alien-mediated repression and to the induction of the endogenous CYP24 promoter [8].

Analytical, diagnostic and therapeutic context of COPS2

• Surprisingly, using both Western blotting and MALDI-analyses, we revealed that these bands are composed of the GST-Alien protein itself [16].

References