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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\u2013CRL activities has remained unclear. In this study, we reveal that the two\n                    <jats:italic>Arabidopsis thaliana<\/jats:italic>\n                    InsP\u2010kinases, IPK1 and ITPK1, physically interact and orchestrate the metabolic regulation of the CSN holo\u2010complex 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\u2010complex. 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\u2010limited wild\u2010type plants and constitutively active in the InsP\u2010kinase 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\u2013CRL dynamics to phosphate sensing. Conversely, pharmacologically inhibiting CSN5 deneddylase activity causes wild\u2010type plants to exhibit PSR phenotypes similar to those of the InsP\u2010kinase mutants. Collectively, these results reveal that specific InsP\u2010kinases are partly involved in modulating plant PSR by fine\u2010tuning the coordination between CRL and CSN activities.\n                  <\/jats:p>","DOI":"10.1111\/jipb.70268","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T06:16:52Z","timestamp":1778048212000},"page":"3569-3592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Arabidopsis inositol polyphosphate kinase activities regulate COP9 deneddylation functions in phosphate homeostasis"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8122-8661","authenticated-orcid":false,"given":"Yashika","family":"Walia","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction and Plant Resistance, UNESCO\u2010Regional Centre for Biotechnology (RCB) NCR Biotech Science Cluster Faridabad 121001 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