2026/05/05 by Yashika Walia, Medha Noopur, Ishana Bhattacharya +10 · 2 voices
Biochemistry, Genetics and Molecular Biology · #Ubiquitin and proteasome pathways #Cellular transport and secretion #Endoplasmic Reticulum Stress and Disease
paper · doi:10.1111/jipb.70268
openalex publication_date 2026/05/05 · openalex created_date 2026/05/07 · openalex updated_date 2026/07/28
Plant Cullin RING Ubiquitin E3 ligases (CRLs) play a critical role in targeted protein degradation, essential for physiological development and stress adaptation. The deneddylase activity of the COP9 signalosome (CSN) tightly regulates the cellular balance of neddylated cullins, which is crucial for maintaining the full spectrum of CRL functions. Although selective inositol polyphosphates (InsPs) act as cofactors in plant responses that involve ubiquitylation of negative regulators, their connection to CSN-CRL activities has remained unclear. In this study, we reveal that the two Arabidopsis thaliana InsP-kinases, IPK1 and ITPK1, physically interact and orchestrate the metabolic regulation of the CSN holo-complex activity. Notably, ITPK1 deficiency lowers Nedd8 processing rates, elevates the cellular ratios of neddylated cullins, and disturbs the dissociation equilibrium of CSN5 and CUL1 from the holo-complex. These findings uncover a novel autoregulatory switch in CSN functions, governed by deneddylation activity. Furthermore, we demonstrate that the phosphate starvation response (PSR), induced in phosphate-limited wild-type plants and constitutively active in the InsP-kinase mutants, is partly regulated by reduced deneddylation rates, which affect the stability of SPX4, a key negative regulator of PSR. Pharmacological inhibition of cullin neddylation stabilizes SPX4 and impairs PSR, thereby linking CSN-CRL dynamics to phosphate sensing. Conversely, pharmacologically inhibiting CSN5 deneddylase activity causes wild-type plants to exhibit PSR phenotypes similar to those of the InsP-kinase mutants. Collectively, these results reveal that specific InsP-kinases are partly involved in modulating plant PSR by fine-tuning the coordination between CRL and CSN activities.