Are Inositol Polyphosphates the Missing Link in Dynamic Cullin RING Ligase Regulation by the COP9 Signalosome?

Zhang, Xiaozhe; Rao, Feng

doi:10.3390/biom9080349

Cited by 10 publications

(7 citation statements)

References 64 publications

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“…Consistently, 5-IP 7 is threefold less potent than IP 6 in stimulating CRL4A-CSN interaction in vitro (18). These results suggest that IP 6 and its metabolic enzymes may mediate stimuliregulated CRL-CSN complex dynamics and CRL activation (20). However, the structural and biochemical basis of IP 6 's action remains unclear.…”

Section: Significancementioning

confidence: 77%

Basis for metabolite-dependent Cullin-RING ligase deneddylation by the COP9 signalosome

Lin

Zhang

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The Cullin-RING ligases (CRLs) are the largest family of ubiquitin E3s activated by neddylation and regulated by the deneddylase COP9 signalosome (CSN). The inositol polyphosphate metabolites promote the formation of CRL–CSN complexes, but with unclear mechanism of action. Here, we provide structural and genetic evidence supporting inositol hexakisphosphate (IP6) as a general CSN cofactor recruiting CRLs. We determined the crystal structure of IP6 in complex with CSN subunit 2 (CSN2), based on which we identified the IP6-corresponding electron density in the cryoelectron microscopy map of a CRL4A–CSN complex. IP6 binds to a cognate pocket formed by conserved lysine residues from CSN2 and Rbx1/Roc1, thereby strengthening CRL–CSN interactions to dislodge the E2 CDC34/UBE2R from CRL and to promote CRL deneddylation. IP6 binding-deficient Csn2K70E/K70E knockin mice are embryonic lethal. The same mutation disabled Schizosaccharomyces pombe Csn2 from rescuing UV-hypersensitivity of csn2-null yeast. These data suggest that CRL transition from the E2-bound active state to the CSN-bound sequestered state is critically assisted by an interfacial IP6 small molecule, whose metabolism may be coupled to CRL–CSN complex dynamics.

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Section: Significancementioning

confidence: 77%

Basis for metabolite-dependent Cullin-RING ligase deneddylation by the COP9 signalosome

Lin

Zhang

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Obviously, contributions made from other fields of science will improve the understanding of the action mechanisms of CSN. First, new methodologies should be encouraged to be utilized in CSN biology, such as chemistry/cryo‐SEM, single‐cell sequencing/mathematical modeling/advanced MS strategy (Rozen et al 2015; Liu et al 2018; Zhang and Rao 2019). Second, functional study of CSN should be updated with progress in the field, for example, whether the presence of CSN in the nuclear is involved in phase separation, and whether CSN is related to the condensates in heterochromatin organization in a similar way as long non‐coding RNA‐mediated para‐speckle formation (Shrinivas et al 2019).…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

COP9 signalosome: Discovery, conservation, activity, and function

Qin

et al. 2020

JIPB

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The COP9 signalosome (CSN) is a conserved protein complex, typically composed of eight subunits (designated as CSN1 to CSN8) in higher eukaryotes such as plants and animals, but of fewer subunits in some lower eukaryotes such as yeasts. The CSN complex is originally identified in plants from a genetic screen for mutants that mimic light-induced photomorphogenic development when grown in the dark. The CSN complex regulates the activity of cullin-RING ligase (CRL) families of E3 ubiquitin ligase complexes, and play critical roles in regulating gene expression, cell proliferation, and cell cycle. This review aims to summarize the discovery, composition, structure, and function of CSN in the regulation of plant development in response to external (light and temperature) and internal cues (phytohormones).

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“…A JAs-mediated induction of inositol pyrophosphate InsP8, which binds to COI1-JAZ co-receptor, was described as part of plant defense response against necrotrophic fungi and herbivorous insects in A. thaliana (Laha et al, 2015). Much more recently, it was demonstrated in animal systems that InsP6 and InsP7, in association with IP5K and IP6K enzymes, participate in the assembly of cullin-RING E3 ubiquitin ligase complexes (Zhang and Rao, 2019). In this context, COI1 putative S-nitrosation could affect COI1 activity by modifying inositol polyphosphates binding.…”

Section: Coronatine Insensitive 1 F-box Protein As a Putative Target ...mentioning

confidence: 99%

S-Nitrosation of E3 Ubiquitin Ligase Complex Components Regulates Hormonal Signalings in Arabidopsis

et al. 2022

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E3 ubiquitin ligases mediate the last step of the ubiquitination pathway in the ubiquitin-proteasome system (UPS). By targeting transcriptional regulators for their turnover, E3s play a crucial role in every aspect of plant biology. In plants, SKP1/CULLIN1/F-BOX PROTEIN (SCF)-type E3 ubiquitin ligases are essential for the perception and signaling of several key hormones including auxins and jasmonates (JAs). F-box proteins, TRANSPORT INHIBITOR RESPONSE 1 (TIR1) and CORONATINE INSENSITIVE 1 (COI1), bind directly transcriptional repressors AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) and JASMONATE ZIM-DOMAIN (JAZ) in auxin- and JAs-depending manner, respectively, which permits the perception of the hormones and transcriptional activation of signaling pathways. Redox modification of proteins mainly by S-nitrosation of cysteines (Cys) residues via nitric oxide (NO) has emerged as a valued regulatory mechanism in physiological processes requiring its rapid and versatile integration. Previously, we demonstrated that TIR1 and Arabidopsis thaliana SKP1 (ASK1) are targets of S-nitrosation, and these NO-dependent posttranslational modifications enhance protein-protein interactions and positively regulate SCFTIR1 complex assembly and expression of auxin response genes. In this work, we confirmed S-nitrosation of Cys140 in TIR1, which was associated in planta to auxin-dependent developmental and stress-associated responses. In addition, we provide evidence on the modulation of the SCFCOI1 complex by different S-nitrosation events. We demonstrated that S-nitrosation of ASK1 Cys118 enhanced ASK1-COI1 protein-protein interaction. Overexpression of non-nitrosable ask1 mutant protein impaired the activation of JA-responsive genes mediated by SCFCOI1 illustrating the functional relevance of this redox-mediated regulation in planta. In silico analysis positions COI1 as a promising S-nitrosation target, and demonstrated that plants treated with methyl JA (MeJA) or S-nitrosocysteine (NO-Cys, S-nitrosation agent) develop shared responses at a genome-wide level. The regulation of SCF components involved in hormonal perception by S-nitrosation may represent a key strategy to determine the precise time and site-dependent activation of each hormonal signaling pathway and highlights NO as a pivotal molecular player in these scenarios.

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Are Inositol Polyphosphates the Missing Link in Dynamic Cullin RING Ligase Regulation by the COP9 Signalosome?

Cited by 10 publications

References 64 publications

Basis for metabolite-dependent Cullin-RING ligase deneddylation by the COP9 signalosome

Basis for metabolite-dependent Cullin-RING ligase deneddylation by the COP9 signalosome

COP9 signalosome: Discovery, conservation, activity, and function

S-Nitrosation of E3 Ubiquitin Ligase Complex Components Regulates Hormonal Signalings in Arabidopsis

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