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The COP9 signalosome: at the interface between signal transduction and ubiquitin-dependent proteolysis

¹ Division of Molecular Biology, Department of Surgery, Medical Faculty Charité, Humboldt University, Monbijoustrasse 2, 10117 Berlin, Germany
² MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

View larger version (37K): [in a new window]   Fig. 1. (a) 2D electron microscopic images of the CSN and the LID. The putative subunit arrangement of the CSN on the basis of the subunit-subunit interaction studies (Kapelari et al., 2000) is indicated. LID subunit-subunit interactions were deduced from CSN data by arranging homologous subunits. The central groove is marked by black arrow. The images were provided by B. Kapelari. (b) CSN interactions with other proteins. The CSN model is based on the electron microscopic image shown in (a) and on subunit-subunit interaction studies summarised recently (Kapelari et al., 2000). Subunits containing MPN domains are blue and those with PCI domains are yellow. The phosphorylation of CSN2 and CSN7 is indicated. All interactions of CSN subunits with other proteins are referenced in Table 1.

View larger version (13K): [in a new window]   Fig. 2. Putative reaction sequence of CSN/proteasome-mediated degradation of the tumour suppressor p53. CSN subunits modified by phosphorylation are indicated by red dots. Under normal growth conditions, p53 is continuously phosphorylated by the CSN-associated kinase. In the reaction scheme, unpublished data are included suggesting that the Ub ligase Mdm2 directly interacts with the CSN and presumably forms a temporary complex that contains p53 (S. Uhle and W. Dubiel, unpublished). Mdm2 might bind to the CSN-p53 complex after phosphorylation and ubiquitinate the tumour suppressor. At the moment, it is unclear how the p53-Ub conjugates are delivered to the 26S proteasome. The 19S regulator of the 26S proteasome consists of the LID and the BASE. In the figure, it is attached to only one side of the 20S proteasome, the proteolytic machinery.