Trying to make sense out of the COP9 signalosome
Daniel A. Chamovitz
Dep't of Plant Sciences

The COP9 signalosome (CSN) is multi-functional protein complex that
functions at the nexus of multiple signaling inputs and regulatory
outputs.  More specifically, CSN impinges on numerous signaling pathways
controlling various aspects of development, including pathways directly
controlling cell cycle, DNA repair, and transcription. Because of the
fundamental nature of these processes, CSN dysfunction has extensive
consequences for human health, and CSN subunits have been correlated
with a number of hereditary diseases and cancers. The complexity and
confusion surrounding CSN function partially arises from its
multi-subunit nature. The CSN core-complex has eight subunits and is
highly conserved in all higher eukaryotes, yet its exact biological role
and mechanism remains enigmatic. Several CSN subunits are found in
multiple biochemical forms, some of which are independent both
structurally and spatially of the CSN core-complex. Adding to the
complexity, CSN interacts with numerous proteins. My lab employs both
Arabidopsis and Drosophila model systems to study the developmental and
biochemical functions of the CSN.  We are using a combination of
genetic, biochemical and genomic approaches to elucidate the specific
mechanisms by which the CSN and its individual subunits regulate
multiple signaling pathways.  Our results show that the CSN is involved
in regulating multiple developmental processes including pattern
formation, hematopoiesis, and cell cycle through regulating such
processes as translation, protein degradation and protein localization.
Transcriptome and bioinformatics analysis has revealed that the
regulation of certain subsets of genes may be temporally shifted due to
mutations in CSN subunits.