Arabidopsis COP9 is a component of a novel signaling complex mediating light control of development.
ABSTRACT Environmental light signals are sensed by multiple families of photoreceptors and transduced by largely unknown mechanisms to regulate plant development. In this report, genetic analysis suggested that light signals perceived by both phytochromes and a blue light receptor converge to repress the action of Arabidopsis COP9 in suppressing seedling photomorphogenesis. Molecular cloning of the gene revealed that COP9 encodes a novel protein of 197 amino acids whose expression is not regulated by light. COP9 functions as a large (> 560 kDa) complex(es) that is probably subjected to light modulation. In addition, COP8 and COP11 are required for either the COP9 complex formation or its stability. Therefore COP9, together with COP8 and COP11, defines a novel signaling step in mediating light control of plant development.
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ABSTRACT: The mammalian COP9 signalosome is an eight-subunit (CSN1–CSN8) complex that plays essential roles in multiple cellular and physiological processes. CSN5 and CSN6 are the only two MPN (Mpr1-Pad1-N-terminal) domain-containing subunits in the complex. Unlike the CSN5 MPN domain, CSN6 lacks a metal-binding site and isopeptidase activity. Here, we report the crystal structure of the human CSN6 MPN domain. Each CSN6 monomer contains nine β sheets surrounded by three helices. Two forms of dimers are observed in the crystal structure. Interestingly, a domain swapping of β8 and β9 strands occurs between two neighboring monomers to complete a typical MPN fold. Analyses of the pseudo metal-binding motif in CSN6 suggest that the loss of two key histidine residues may contribute to the lack of catalytic activity in CSN6. Comparing the MPN domain of our CSN6 with that in the CSN complex shows that apart from the different β8–β9 conformation, they have minor conformational differences at two insertion regions (Ins-1 and Ins-2). Besides, the interacting mode of CSN6–CSN6 in our structure is distinct from that of CSN5–CSN6 in the CSN complex structure. Moreover, the functional implications for Ins-1 and Ins-2 are discussed.Biochemical and Biophysical Research Communications 09/2014; 453(1). DOI:10.1016/j.bbrc.2014.09.046 · 2.28 Impact Factor
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ABSTRACT: Fungal genomics revealed a large potential of yet-unexplored secondary metabolites, which are not produced during vegetative growth. The discovery of novel bioactive compounds is increasingly gaining importance. The high number of resistances against established antibiotics requires novel drugs to counteract increasing human and animal mortality rates. In addition, growth of plant pathogens has to be controlled to minimize harvest losses. An additional critical issue is the post-harvest production of deleterious mycotoxins. Fungal development and secondary metabolite production are linked processes. Therefore, molecular regulators of development might be suitable to discover new bioactive fungal molecules or to serve as targets to control fungal growth, development, or secondary metabolite production. The fungal impact is relevant as well for our healthcare systems as for agriculture. We propose here to use the knowledge about mutant strains discovered in fungal model systems for a broader application to detect and explore new fungal drugs or toxins. As examples, mutant strains impaired in two conserved eukaryotic regulatory complexes are discussed. The COP9 signalosome (CSN) and the velvet complex act at the interface between development and secondary metabolism. The CSN is a multi-protein complex of up to eight subunits and controls the activation of CULLIN-RING E3 ubiquitin ligases, which mark substrates with ubiquitin chains for protein degradation by the proteasome. The nuclear velvet complex consists of the velvet-domain proteins VeA and VelB and the putative methyltransferase LaeA acting as a global regulator for secondary metabolism. Defects in both complexes disturb fungal development, light perception, and the control of secondary metabolism. The potential biotechnological relevance of these developmental fungal mutant strains for drug discovery, agriculture, food safety, and human healthcare is discussed.Applied Microbiology and Biotechnology 08/2014; 98(20). DOI:10.1007/s00253-014-5997-8 · 3.81 Impact Factor
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ABSTRACT: COP9 signalosome (CSN), which is originally identified as the regulator of the photomorphogenic development in plant, is highly conserved protein complex in diverse eukaryotic organisms. Most eukaryotic CSN complex is composed of 8 subunits, which is structurally and functionally similar to the lid subunit of 26S proteasome and eIF3 translation initiation complex. CSN play important functions in the regulation of cell cycle and checkpoint response by controlling Cullin-Ring E3 ubiquitin ligases (CRL) activities. CSN exhibits an isopeptidase activity which cleaves the neddylated moiety of cullin components. In fission yeast, S-phase cell cycle progression was delayed and the sensitivity to g-ray or UV was increased in CSN1 and CSN2 deletion mutants, indicating that yeast CSN is also involved in the checkpoint regulation. CSN in fungal system more closely resembles that of the higher organisms in the structure and assembly of their components. Functionally, CSN is associated with the regulation of conidiation rhythms in Neurospora crassa and the sexual development in Aspsergillus nidulans. Recent studies also revealed that CSN functions as an essential cell cycle regulator, playing key roles in the regulation of DNA replication and DNA damage response in Aspergillus. Overall, CSN of microorganisms, such as fission yeast and fungi, share functionally common aspects with higher organisms, implying that they can be useful tools to study the role of CSN in the CRL-mediated diverse cellular activities.03/2013; 41(1). DOI:10.4489/KJM.2013.41.1.1