COPS5, NT (COP9 Signalosome Complex Subunit 5, SGN5, Signalosome Subunit 5, Jun Activation Domain-binding Protein 1, CSN5, JAB1)

The COP9 Signalosome (CSN) is a ubiquitously expressed multiprotein complex that is involved in a vast array of cellular and developmental processes, which is thought to be attributed to its control over the ubiquitin-proteasome pathway. Typically, the CSN is composed of eight highly conserved subunits (CSN1-CSN8), each of which is homologous to one of the eight subunits that form the lid of the 26S proteasome particle, suggesting that these complexes have a common evolutionary ancestor (1). CSN was first identified in Arabidopsis thaliana mutants with a light-grown seedling phenotype when grown in the dark (2-4). The subsequent cloning of the constitutive morphogenesis 9 (cop9) mutant from Arabidopsis thaliana was soon followed by the biochemical purification of the COP9-containing multiprotein complex (4). It is now widely accepted that the CSN directly interacts with cullin-RING ligase (CRL) families of ubiquitin E3 complexes, and that CSN is required for their proper function (5). In addition, CSN may also regulate protein homeostasis through its association with protein kinases and deubiquitylating enzymes. Collectively, these activities position the CSN as a pivotal regulator of the DNA-damage response, cell-cycle control, and gene expression (1). COPS5/CSN5/Jab1 (c-Jun activation domain-binding protein-1) was originally identified as a transcriptional coactivator of c-Jun and subsequently discovered to be a fifth component and integral part of the CSN (6). As the catalytic center of the CSN, COPS5 is able to integrate multiple functions of the CSN complex such as cell-cycle control, transcription, and DNA-damage response by regulating the activity of CRLs through deneddylation of cullins (7). Indeed, COPS5 harbors a Mpr1-Pad1-N-terminal (MPN) domain with an embedded Jab1/CSN5 MPN domain metalloenzyme (JAMM) motif that is essential for the CSN isopeptidase activity responsible for deneddylation of CRLs. COPS5 is an evolutionarily conserved 38kD protein in humans, mice, fission yeast, and plants, which suggests that it is critical to cell survival and proliferation. A role for COPS5 as a positive regulator of cellular proliferation is supported by evidence that it functionally inactivates several key tumor suppressors such as p53, RUNX3, Smad4, and p27Kip1 through altered subcellular localization, degradation, and deneddylation (8-12). These findings are underscored by the observation that COPS5 overexpression has been identified in a number of different tumor types and has been implicated in the initiation and progression of several types of cancer (13). Moreover, COPS5-deficient mice display an embryonically lethal phenotype highlighted by elevated expression of COPS5 targets such as p53 and p27 (14,15). Applications: Suitable for use in Immunofluorescence, Western Blot and Immunoprecipitation. Other applications not tested. Recommended Dilution: Immunofluorescence (IF-IC): 1:50 Western Blot: 1:1000 Immunoprecipitation: 1:50 Optimal dilutions to be determined by the researcher. Storage and Stability: May be stored at 4 degrees C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.