Disease relevance of Cops5

• The neuronal POU transcription factor Brn-2 interacts with Jab1, a gene involved in the onset of neurodegenerative diseases [1].
• Considering the involvement of Jab1 in the onset of the neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, the interaction between Brn-2 and Jab1 may provide some insights into the understanding of neuronal development and neurodegenerative diseases [1].
• Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors [2].
• No difference was found in Jab1 protein levels in either corticotroph tumors or other pituitary adenomas, compared with normal tissue, but there was a small but significant increase in Jab1 levels in carcinomas [2].
• Depletion of Jab1 inhibits proliferation of pancreatic cancer cell lines [3].

High impact information on Cops5

• Psoriasin interacts with Jab1 and influences breast cancer progression [4].
• Jab1+/- mouse embryonic fibroblast cells, in which the amount of Jab1-containing small subcomplex, but not that of CSN, was selectively reduced, proliferated poorly, showed an inefficient down-regulation of p27 during G1, and was delayed in the progression from G0 to S phase by 3 h compared with the wild-type cells [5].
• Multiple functions of Jab1 are required for early embryonic development and growth potential in mice [5].
• Thus, Jab1 controls cell cycle progression and cell survival by regulating multiple cell cycle signaling pathways [5].
• To elucidate the function of Jab1, we targeted the Jab1 locus by homologous recombination in mouse embryonic stem cells [5].

Biological context of Cops5

• In addition, a high level of Jab1 is observed in a variety of human cancers and is sometimes correlated with a poor prognosis, suggesting that Jab1 contributes to cancer cell proliferation and survival and could be a novel target of cancer therapy [6].
• We obtained Jun-activation-domain-binding protein 1 (Jab1) as a new Brn-2 binding protein [1].
• These results indicate that cytoplasmic shuttling regulated by Jab1/CSN5 and other CSN components may be a new pathway to control the intracellular abundance of the key cell cycle regulator [7].
• Alteration of conserved leucine residues to alanine within Jab1/CSN5-NES abolished the interaction with CRM1 in vitro and impaired LMB-sensitive nuclear export and the ability to induce p27 breakdown in cultured cells [7].
• Here we describe experiments that showing phosphorylation of p27(Kip1) at serine 10 leads to the suppression of Jab1 levels with the concomitant inhibition of c-Jun-dependent transcription [8].

Anatomical context of Cops5

• In the adult brain, additional areas of JAB1/CSN5 expression were the hippocampus and the Purkinjie layer of the cerebellum [9].
• Preferential expression in selected tissues was detected starting at E11.5, with higher levels in dorsal root ganglia; at later stages, prominent expression of JAB1/CSN5 transcripts was observed in cranial nerve, spinal and sympathetic ganglia, as well as in selected epithelia, such as the oral and the olfactory epithelium [9].
• When Jab1 expression and lymph node status are combined, patients with Jab1(+)/lymph node(+) revealed poorer disease-free andoverall survival than others (P < 0.0001 and P < 0.0001, respectively) [10].

Associations of Cops5 with chemical compounds

• Glycerol gradient and cell fractionation experiments showed that at least two different forms of Jab1/CSN5-containing complexes existed within the cell [7].
• Nuclear-cytoplasmic translocation plays an important role because leptomycin B (LMB), a chemical inhibitor of CRM1-dependent nuclear export, prevents p27 degradation mediated by Jab1/CSN5 [7].

Physical interactions of Cops5

• Additional far Western and pull-down studies with Id3 support our two-hybrid data and show that the transcription regulator can bind to CSN5 and CSN7 [11].

Other interactions of Cops5

• Direct interaction between Brn-2 and Jab1 was confirmed by using a surface plasmon resonance biosensor [1].
• Small Jab1-containing subcomplex is regulated in an anchorage- and cell cycle-dependent manner, which is abrogated by ras transformation [12].

References