The COP9 signalosome (CSN) is a multimeric protein complex, comprising eight subunits, that occurs in all eukaryotic cells.
Overview on the COP9 Signalosome (CSN Complex)
The CSN complex (COP9 signalosome) was originally identified as a regulator of light-mediated development in Arabidopsis that, when mutated, caused signal-independent expression of light-induced genes (thus COP, constitutive photomorphogenesis). In mammals the CSN has been found to play a significant role in cellular processes such as cell signaling, cell cycle progression, gene transcription, cell survival, and DNA repair. The CSN is comprised of eight subunits, CSN1 through CSN8, and functions as an interface between cellular signals and the regulation of ubiquitin-dependent degradation of proteins.
The CSN appears to accomplish its functions through its metalloproteinase and kinase activities. As a metalloproteinase, CSN functions to cleave Nedd8 from cullin-based E3-ubiquitin ligase (Cul-E3). Removal of Nedd8 is necessary for the recycling and maintenance of Cul-E3 for further rounds of ubiquitination of target substrates, and thus regulates Cul-E3 ligase-mediated degradation of cellular proteins. Through its associated kinase activity, CSN phosphorylates signal transducers such as I-kappa-B-alpha, p105, and c-Jun, and the tumor suppressor p53. The phosphorylation of c-Jun and p53 directly relate to their stability in the ubiquitin-proteasomal pathway.
The CSN has emerged as an important subject of study due to the finding that ubiquitin-mediated regulation of proteins is critical to a variety of cellular processes. Additionally, both the CSN and the ubiquitin-proteasome pathway are implicated in the development of human disease and cancer. A better understanding of the roles of the individual CSN subunits, the relevance of interacting proteins, and the enzymatic activities of the CSN will allow a better evaluation of the value of the CSN as a therapeutic target.
Bethyl Laboratories COP9 Signalosome (CSN) Antibody Portfolio
Characterization of CSN from yeast to mammals reveals its function as a modulator of signal transduction pathways involved in a variety of cellular and developmental processes. One of the major functions of the CSN is the regulation of protein degradation via intersection with the ubiquitin-proteasome pathway and regulation of E3-ubiquitin ligases. CSN also possesses kinase activity.
Alternate designations for CSN1 include COP9 signalosome complex subunit 1, signalosome subunit 1, SGN1, JAB1-containing signalosome subunit 1, G protein pathway suppressor 1, protein GPS1, protein MFH, GPS1, COPS1, and MGC71287.
CSN2 has also been demonstrated to interact with the sin3A corepressor complex as well as the thyroid hormone and vitamin D3 receptor to mediate gene repression. Alternate designations for CSN2 include COP9 signalosome complex subunit 2, signalosome subunit 2, SGN2, JAB1-containing signalosome subunit 2, thyroid receptor-interacting protein 15, TRIP-15, Alien homolog, COPS2, TRIP15, and SGN2.
CSN3 is the kinase associated with the CSN complex that phosphorylates signal transducers such as I-kappa-Balpha, p105, and c-Jun. Human CSN3 maps to the Smith-Magenis syndrome locus. Microdeletions in this locus results in mental retardation, skeletal abnormalities, sleep disorder, and neurobehavior anomalies. Alternate designations for CSN3 include COP9 signalosome complex subunit3, signalosome subunit 3, SGN3, JAB1-containing signalosome subunit 3, and COPS3.
Alternate designations for CSN4 include COP9 signalosome complex subunit 4, signalosome subunit 4, SGN4, JAB1-containing signalosome subunit 4, COPS4, MGC10899, and MGC15160.
CSN5 has been identified as the subunit that functions to remove Nedd8, an ubiquitin-like modifier, from cullin-based E3-ubiquitin ligases. CSN5 also functions as a coactivator of nuclear receptors. Alternate designations for CSN5 include COP9 signalosome complex subunit 5, signalosome subunit 5, SGN5, jun activation domain-protein 1, COPS5, JAB1, MOV-34, and MGC3149.
Alternate identifiers of CSN7b include COP9 signalosome complex subunit 7b, signalosome subunit 7b, SGN7b, JAB1-containing signalosome subunit 7b, COPS7B, FLJ12612, and MGC111077.
RabMAb to CSN7A