JAB1/CSN5 and the COP9 signalosome. A complex situation

Abstract

The Jun activating binding protein (JAB1) specifically stabilizes complexes of c-Jun or JunD with AP-1 sites, increasing the specificity of target gene activation by AP-1 proteins. JAB1 is also known as COP9 signalosome subunit 5 (CSN5), which is a component of the COP9 signalosome regulatory complex (CSN). Over the past year, JAB1/CSN5 has been implicated in numerous signaling pathways including those that regulate light signaling in plants, larval development in Drosophila, and integrin signaling, cell cycle control, and steroid hormone signaling in a number of systems. However, the general role of the CSN complex, and the specific role of JAB1/CSN5, still remain obscure. This review attempts to integrate the available data to help explain the role of JAB1/CSN5 and the COP9 signalosome in regulating multiple pathways (in this review, both JAB1 and CSN5 terminologies are used interchangeably, depending on the source material).

Fig. 1. Model of COP9 signalosome (CSN) function in photomorphogenesis. In the absence of light signals, the CSN represses photomorphogenesis (Light) leading to dark-grown (Dark) growth patterns (wt, left). Part of the repression is mediated through the degradation of the HY5 transcription factor (not shown). Light signals transduced from the photoreceptors lead to a release of this repression. Mutations in the CSN lead to constitutive photomorphogenesis (cop) in the dark. A representative dark-grown cop mutant, and dark- and light-grown wild-type (wt), Arabidopsis seedlings are shown.

Fig. 2. Model of JAB1/CSN5 function in p27^Kip1 mediated cell cycle control. Thin lines ending with filled circles represent inhibitory interactions. Thin lines ending with closed arrow heads represent stimulatory interactions. Dotted lines show protein movement. Binding of p27^Kip1 to JAB1 leads to cell cycle progression, and the concomitant export of p27^Kip1 from the nucleus and its degradation. Binding of JAB1 to MIF allows the nuclear accumulation of p27^Kip1 and cell cycle arrest. The protein–protein interactions within the CSN are not specified (reviewed in Kapelari et al., 2000). CSN, COP9 signalosome.

Fig. 3. Model of JAB1/CSN5 function in regulating AP-1 mediated transcription. Line colors relate to specific functions: blue, c-Jun mediated transactivation; pink, hormone receptor mediated transactivation. Thin lines ending with filled circles represent inhibitory interactions. Thin lines ending with closed arrow heads represent stimulatory interactions. Dotted lines show protein movement. JAB1/CSN5 mediates AP-1 transactivation through c-Jun. Interaction of JAB1 with LFA-1, MIF or LHR inhibits AP-1 transactivation. Extracellular substrate binding to LFA-1 releases JAB1 which redistributes to the nucleus leading to AP-1 transactivation. Binding of JAB1/CSN5 to PR and SRC-1 also induces AP-1 transactivation. The protein–protein interactions within the CSN are not specified (reviewed in Kapelari et al., 2000). CSN, COP9 signalosome.

Daniel A. Chamovitz & Daniel Segal