Inositol 1,3,4-Trisphosphate 5/6-Kinase Associates with the COP9 Signalosome by Binding to CSN1

Abstract

The COP9 signalosome (CSN) is a complex of eight proteins first identified as a repressor of plant photomorphogenesis. A protein kinase activity associated with the COP9 signalosome has been reported but not identified; we present evidence for inositol 1,3,4-trisphosphate 5/6-kinase (5/6-kinase) as a protein kinase associated with the COP9 signalosome. We have shown that 5/6-kinase exists in a complex with the eight-component COP9 signalosome both when purified from bovine brain and when transfected into HEK 293 cells. 5/6-kinase phosphorylates the same substrates as those of the COP9 signalosome, including IB␣, p53, and c-Jun but fails to phosphorylate several other substrates, including c-Jun 1-79, which are not substrates for the COP9-associated kinase. Both the COP9 signalosomeassociated kinase and 5/6-kinase are inhibited by curcumin. The association of 5/6-kinase with the COP9 signalosome is through an interaction with CSN1, which immunoprecipitates with 5/6-kinase. In addition, the inositol kinase activity of 5/6-kinase is inhibited when in a complex with CSN1. We propose that 5/6-kinase is the previously described COP9 signalosome-associated kinase.

CSN1 inhibits c-Jun phosphorylation and down-regulates ectopic expression of JNK1

“…Here we show that CSN1 inhibits UV and MEKK1 induced c-Jun phosphorylation, represses c-Jun dependent transcription activity, and silences ectopic expression of JNK1. In addition to our findings, CSN1 has been shown to bind 5/6-kinase and inhibit its kinase activity in c-Jun phosphorylation (Sun et al, 2002). Together, these results demonstrate that CSN1 has a negative impact on the AP-1 pathway.…”

“…We showed that CSN1 can repress UV and serum induced expression of c-fos-lacZ chimeric gene in mouse fibroblast cells (Tsuge et al, 2001). In addition, CSN1 was shown to mediate interaction of CSN complex with 5/6-kinase, which can phosphorylate c-Jun and ATF-2 (Wilson et al 2001;Sun et al 2002). Moreover, ectopic expression of CSN1 was shown to inhibit the CSN-associated 5/6-kinase activity (Sun et al, 2002).…”

Inositol 1,3,4-Trisphosphate 5/6-Kinase Inhibits Tumor Necrosis Factor-induced Apoptosis

“…The COP9 signalosome has been implicated in regulation of the cell cycle, proteolysis in the proteasome, and plant development (11)(12)(13). We have shown that 5/6-kinase associates with the CSN1 subunit of the COP9 signalosome and phosphorylates I B␣ and c-Jun (9,10). I B␣ phosphorylation is an important regulatory mechanism for TNF␣ 1 -induced NF-B activation.…”

“…In addition, 5/6-kinase has been reported to phosphorylate inositol 3,4,5,6-tetrakisphosphate to inositol 1,3,4,5,6-pentakisphosphate (8). Recently, we have reported that 5/6-kinase also exhibits protein kinase activity and associates with the COP9 signalosome complex (9,10). The COP9 signalosome has been implicated in regulation of the cell cycle, proteolysis in the proteasome, and plant development (11)(12)(13).…”

Akyrin repeat and SOCS box containing protein 4 (Asb-4) interacts with GPS1 (CSN1) and inhibits c-Jun NH2-terminal kinase activity

“…CSN has also been shown to interact with protein kinases and to affect kinase activity [19]. Sun et al reported that inositol 1,3,4,-trisphosphate 5/6-kinase associates with CSN through an interaction with CSN1 (GPS1) and that overexpression of CSN1 inhibited 5/6 kinase activity [20]. Spain et al reported that overexpression of GPS1 in NIH 3T3 cell repressed JNK1 activity [21].…”