title: Dynamic regulation of the COP9 signalosome in response to DNA damage.
abstract: The COP9 signalosome (CSN) is an evolutionarily conserved protein complex that participates in the regulation of the ubiquitin/26S proteasome pathway by controlling the function of cullin-RING-ubiquitin ligases. Impressive progress has been made in deciphering its critical role in diverse cellular and developmental processes. However, little is known about the underlying regulatory principles that coordinate its function. Through biochemical and fluorescence microscopy analyses, we determined that the complex is localized in the cytoplasm, nucleoplasm, and chromatin-bound fractions, each differing in the composition of posttranslationally modified subunits, depending on its location within the cell. During the cell cycle, the segregation between subcellular localizations remains steady. However, upon UV damage, a dose-dependent temporal shuttling of the CSN complex into the nucleus was seen, accompanied by upregulation of specific phosphorylations within CSN1, CSN3, and CSN8. Taken together, our results suggest that the specific spatiotemporal composition of the CSN is highly controlled, enabling the complex to rapidly adapt and respond to DNA damage.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Füzesi-Levi
authors.forename: Gili
authors.initials: G
authors.lastname: Ben-Nissan
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bianchi
authors.forename: Houjiang
authors.initials: H
authors.lastname: Zhou
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Deery
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Lilley
authors.forename: Yishai
authors.initials: Y
authors.lastname: Levin
authors.forename: Michal
authors.initials: M
authors.lastname: Sharon
mesh_terms: D000075686:COP9 Signalosome Complex; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D003593:Cytoplasm / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*
chemical_list: D002843:Chromatin; D046912:Multiprotein Complexes; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex