The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p

Zhou, Chunlan; Seibert, Volker; Geyer, Rory; Rhee, Edward K.; Lyapina, Svetlana; Cope, Greg; Deshaies, Raymond J.; Wolf, David E.

doi:10.1186/1471-2091-2-7

Cited by 101 publications

(14 citation statements)

References 34 publications

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“…Nedd8 is a small ubiquitin-like protein that is conjugated to the K720 residue of Cul-1 (and to an homologous lysine in all other Cullins as well) using Uba3 (E1), Ubc12 (E2), and Roc1 (E3) [28] , [29] , [30] , [31] . This modification is in turn cleaved off by the multi-subunit COP9 Signalosome (CSN) [32] , [33] . Since mutations in the pathways that conjugate and remove Nedd8 are detrimental, the current model is that cycles of neddylation and de-neddylation are necessary for the proper function of CDL [34] , [35] , [36] .…”

Section: Resultsmentioning

confidence: 99%

Identifying Determinants of Cullin Binding Specificity Among the Three Functionally Different Drosophila melanogaster Roc Proteins via Domain Swapping

2008

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BackgroundCullin-dependent E3 ubiquitin ligases (CDL) are key regulators of protein destruction that participate in a wide range of cell biological processes. The Roc subunit of CDL contains an evolutionarily conserved RING domain that binds ubiquitin charged E2 and is essential for ubiquitylation. Drosophila melanogaster contains three highly related Roc proteins: Roc1a and Roc2, which are conserved in vertebrates, and Roc1b, which is specific to Drosophila. Our previous genetic data analyzing Roc1a and Roc1b mutants suggested that Roc proteins are functionally distinct, but the molecular basis for this distinction is not known.Methodology/Principal FindingsUsing co-immunoprecipitation studies we show that Drosophila Roc proteins bind specific Cullins: Roc1a binds Cul1-4, Roc1b binds Cul3, and Roc2 binds Cul5. Through domain swapping experiments, we demonstrate that Cullin binding specificity is strongly influenced by the Roc NH2-terminal domain, which forms an inter-molecular β sheet with the Cullin. Substitution of the Roc1a RING domain with that of Roc1b results in a protein with similar Cullin binding properties to Roc1a that is active as an E3 ligase but cannot complement Roc1a mutant lethality, indicating that the identity of the RING domain can be an important determinant of CDL function. In contrast, the converse chimeric protein with a substitution of the Roc1b RING domain with that of Roc1a can rescue the male sterility of Roc1b mutants, but only when expressed from the endogenous Roc1b promoter. We also identified mutations of Roc2 and Cul5 and show that they cause no overt developmental phenotype, consistent with our finding that Roc2 and Cul5 proteins are exclusive binding partners, which others have observed in human cells as well.ConclusionsThe Drosophila Roc proteins are highly similar, but have diverged during evolution to bind a distinct set of Cullins and to utilize RING domains that have overlapping, but not identical, function in vivo.

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Section: Resultsmentioning

confidence: 99%

Identifying Determinants of Cullin Binding Specificity Among the Three Functionally Different Drosophila melanogaster Roc Proteins via Domain Swapping

2008

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“…The COP9 signalosome (CSN), a conserved eight-protein complex, is a major regulator of the Cullin-RING-based ubiquitin ligases [25] , [26] , [27] . CSN controls Cullin-based ubiquitin ligases by removing the Nedd8 modification from the Cullin component of the ligase [28] , [29] , [30] , [31] .…”

Section: Introductionmentioning

confidence: 99%

COP9 Limits Dendritic Branching via Cullin3-Dependent Degradation of the Actin-Crosslinking BTB-Domain Protein Kelch

Djagaeva

Doronkin

2009

PLoS ONE

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Components of the COP9 signalosome (CSN), a key member of the conserved 26S proteasome degradation pathway, have been detected to be altered in patients of several debilitating syndromes. These findings suggest that CSN acts in neural circuits, but the exact function of CSN in brain remains unidentified. Previously, using Drosophila peripheral nervous system (PNS) as a model system, we determined that CSN is a critical regulator of dendritic morphogenesis. We found that defects in CSN led to the strikingly contrast phenotype of either reducing or stimulating dendritic branching. In particular, we have reported that CSN stimulates dendritic branching via Cullin1-mediated proteolysis. Here we describe that CSN inhibits dendritic arborization in PNS neurons acting via control of Cullin3 function: loss of Cullin3 causes excessive dendritic branching. We also identified a downstream target for Cullin3-dependent degradation in neurons – the actin-crosslinking BTB-domain protein Kelch. Inappropriate accumulation of Kelch, either due to the impaired Cullin3-dependent turnover, or ectopic expression of Kelch, leads to uncontrolled dendritic branching. These findings indicate that the CSN pathway modulates neuronal network in a multilayer manner, providing the foundation for new insight into the CSN role in human mental retardation disorders and neurodegenerative disease.

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“…Reduction in function of different CSN subunits leads to different phenotypes which may indicate that each CSN subunits has unique roles [4,5,27]. Thus, CSN’s function can be regulated by engineering particular subunits [28]. The following sections review data available for the reported hypomorphic mutants of CSN subunits.…”

Section: Characteristics Of Csn Hypomorphic Mutants and Their Impomentioning

confidence: 99%

Role of Cop9 Signalosome Subunits in the Environmental and Hormonal Balance of Plant

Singh

Chamovitz

2019

Biomolecules

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The COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) is a highly conserved protein complex that influences several signaling and developmental processes. The COP9 signalosome consists of eight subunits, among which two subunits, CSN5 and CSN6, contain an Mpr1/Pad1 N-terminal (MPN) domain and the remaining six subunits contain a proteasome, COP9 signalosome, and initiation factor 3 (PCI) domain. In plants, each MPN subunit is encoded by two genes, which is not the case in other organisms. This review aims to provide in-depth knowledge of each COP9 signalosome subunit, concentrating on genetic analysis of both partial and complete loss-of-function mutants. At the beginning of this review, the role of COP9 signalosome in the hormonal signaling and defense is discussed, whereas later sections deal in detail with the available partial loss-of-function, hypomorphic mutants of each subunit. All available hypomorphic mutants are compared based on their growth response and deneddylation activity.

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The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p

Cited by 101 publications

References 34 publications

Identifying Determinants of Cullin Binding Specificity Among the Three Functionally Different Drosophila melanogaster Roc Proteins via Domain Swapping

Identifying Determinants of Cullin Binding Specificity Among the Three Functionally Different Drosophila melanogaster Roc Proteins via Domain Swapping

COP9 Limits Dendritic Branching via Cullin3-Dependent Degradation of the Actin-Crosslinking BTB-Domain Protein Kelch

Role of Cop9 Signalosome Subunits in the Environmental and Hormonal Balance of Plant

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