Revisiting the COP9 signalosome as a transcriptional regulator

Abstract

The COP9 signalosome (CSN) is a highly conserved protein complex that was originally described as a repressor of light-dependent growth and transcription in Arabidopsis. The most studied CSN function is the regulation of protein degradation, which occurs primarily through the removal of the ubiquitin-like modifier Nedd8 from cullin-based E3 ubiquitin ligases. This activity can regulate transcription-factor stability and, therefore, transcriptional activity. Recent data suggest that the CSN also regulates transcription on the chromatin by mechanisms that are not yet clearly understood. Furthermore, the CSN subunits CSN5 and CSN2 seem to act as transcriptional coactivators and corepressors, respectively. Here, I re-evaluate the mechanisms by which the CSN acts as a transcriptional regulator, and suggest that they could extend beyond the regulation of protein stability.

Figure 1

Dynamic equilibrium among the eight-subunit CSN core complex, partial complexes and subunit monomers. Not all partial complexes or monomers are known or shown, and the composition of the partial complexes is probably both tissue and organism specific. The CSN4–CSN8 complex was described in human cells as the JAC (Tomoda et al, 2002). The size of each ball is proportional to the relative protein size. The subunit arrangement is shown according to Sharon et al (2009). The green balls represent PCI-containing subunits and the red balls represent MPN-containing subunits. CSN, COP9 signalosome; JAC, Jab1-associated complex; MPN, MPR1p and PAD1p amino-terminal; PCI, proteasome-COP9-eukaryotic initiation factor 3.

Daniel A. Chamovitz