COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) is a

protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein c ...

with

isopeptidase An isopeptidase is a protease enzyme that hydrolyzes isopeptide bonds, or amide bonds that occur outside the main chain in a polypeptide chain. In protein degradation Isopeptide bonds occur in the linkage of protein amino acid side chains to pro ...

activity. It catalyses the hydrolysis of

NEDD8 NEDD8 is a protein that in humans is encoded by the ''NEDD8'' gene. (in ''saccharomyces cerevisiae'' this protein is known as Rub1) This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a proc ...

protein from the cullin subunit of Cullin-RING ubiquitin ligases (CRL). Therefore, it is responsible for CRL deneddylation – at the same time, it is able to bind denedyllated cullin-RING complex and retain them in deactivated form. COP9 signalosome thus serves as a sole deactivator of CRLs. The complex was originally identified in plants, and subsequently found in all eukaryotic organisms including human. Human COP9 signalosome (total size ~350

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...

) consists of 8 subunits - CSN1,

CSN2 Beta-casein is a protein that in humans is encoded by the ''CSN2'' gene. It is in the class of phosphoproteins and generally occurs in mammalian Mammals () are a group of vertebrate animals constituting the class (biology), class Mamma ...

, CSN3, CSN4, CSN5, CSN6, CSN7 (

COPS7A COP9 signalosome complex subunit 7a is a protein that in humans is encoded by the ''COPS7A'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gene ...

, COPS7B), CSN8. All are essential for full function of the complex and mutation in some of them is lethal in mice.

COP9 signalosome as a drug target for cancer and parasitic infections

Given the essential functions of the COP9 signalosome, the complex has been explored as a target for drug discovery. Preclinical studies showed that inhibiting COP9 resulted in death of cancer cells and medically important parasite.

COP9 signalosome as a drug target for cancer and parasitic infections

References

Further reading