Characterization of Human Constitutive Photomorphogenesis Protein 1, a RING Finger Ubiquitin Ligase That Interacts with Jun Transcription Factors and Modulates Their Transcriptional Activity

Bianchi, Elisabetta; Denti, Simona; Catena, Raffaella; Rossetti, Grazisa; Polo, Simona; Gasparian, Sona; Putignano, Stella; Rogge, Lars; Pardi, Ruggero

doi:10.1074/jbc.m212681200

Cited by 96 publications

(116 citation statements)

References 53 publications

(50 reference statements)

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“…Co-immunoprecipitation experiments show that the most likely explanation for the observed functional downregulation of FL COP1 by COP1D is that the latter heterodimerizes with the former and the resulting heterodimers are unable to stably associate with the other component elements of the COP1-containing E3 ligase complex, as previously suggested for AtCOP1 (Torii et al, 1998; Subramanian The functional effect of COP1D at sub-stoichiometric concentrations can be explained if under the conditions used COP1 levels are limiting to achieve significant degradation of the substrate. This could be due to the extremely short half-life of the COP1 protein (Torii et al, 1998;Bianchi et al, 2003), which can be barely detected in unstimulated cells. The increased steady-state level of endogenous c-Jun and p53 in cells ectopically expressing COP1D provides a further line of evidence supporting a functional role for COP1D.…”

Section: Discussionmentioning

confidence: 99%

“…Forty-eight hours after transfection the cells were harvested and processed according to Bianchi et al (2003). Immunoblotting was performed with anti-Flag (M5, Sigma-Aldrich, St Louis, MO, USA), anti-c-Jun (BD Transduction Laboratories, San Diego, CA, USA), anti-HSV-tag (Novagen, Merck Darmstadt, Germany), anti-T7-tag (Novagen) antibodies and anti-actin (Sigma-Aldrich) for normalization.…”

Section: Methodsmentioning

confidence: 99%

“…The E3 ubiquitin ligase COP1 has recently been shown to recognize selected Jun family members as well as p53 as specific substrates in mammalian cells (Bianchi et al, 2003;Wertz et al, 2004;Dornan et al, 2004b), although the physiological context in which it operates in higher organisms is still unclear. It was established early on that Arabidopsis thaliana COP1 (AtCOP1) functions as an essential negative regulator of light-mediated plant development (Yi and Deng, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Notably, HY5, the preferred substrate of AtCOP1, is a basic region leucine zipper transcription factor that shares with selected Jun family members the structural motifs involved in COP1 binding (Yi and Deng, 2005). Although COP1 is capable of self-ubiquitinating efficiently in vitro (Bianchi et al, 2003), it appears to require the cooperation of other factors in mediating ubiquitination of c-Jun in vivo. It has been suggested that mammalian COP1 functions as an adaptor protein recruiting c-Jun to an E3 complex containing DET1, DDB1, cullin4A and Roc1, through direct interaction with DET1 (Wertz et al, 2004;Yanagawa et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that mammalian COP1 functions as an adaptor protein recruiting c-Jun to an E3 complex containing DET1, DDB1, cullin4A and Roc1, through direct interaction with DET1 (Wertz et al, 2004;Yanagawa et al, 2004). Mammalian COP1 directly associates with c-Jun and represses AP-1-mediated transcription (Bianchi et al, 2003;. The structural requirements for polyubiquitination of p53 by COP1 are less well defined but may differ from those involved in c-Jun degradation, as it has been shown that integrity of the COP1 RING domain, which is dispensable for the degradation of c-Jun, is instead required for p53 ubiquitination and degradation (Wertz et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1) product, stabilizes UV stress-induced c-Jun through inhibition of full-length COP1

et al. 2007

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COP1 is an evolutionarily conserved RING-finger ubiquitin ligase acting within a Cullin-RING ligase (CRL) complex that promotes polyubiquitination of c-Jun and p53. Stability of the above substrates is affected by posttranslational changes priming the proteins for polyubiquitination and proteasome-dependent degradation. However, degradation of both substrates is controlled indirectly by signaling pathways affecting the E3 ligases involved in their polyubiquitination. Here, we report the identification of COP1D, a ubiquitously expressed splice variant of COP1 lacking a portion of a coiled-coil region involved in intermolecular associations. While being unable to associate with other components of the CRL complex, COP1D exerts a dominant-negative function over the full-length protein, due to its ability to heterodimerize with COP1 and sequester it from the enzymatically active complex. Ectopic expression of COP1D antagonizes the function of COP1, while its selective downregulation by RNA interference promotes more efficient degradation of c-Jun and p53 by the full-length protein. The COP1/COP1D mRNA ratio is modulated by UV stress and a decreased COP1/COP1D ratio correlates with elevated c-Jun, but not p53 protein levels in invasive ductal breast cancer. Thus, dynamic changes of the COP1/COP1D ratio provide an additional level of regulation of the half-life of the substrates of this E3 ligase under homeostatic or pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1) product, stabilizes UV stress-induced c-Jun through inhibition of full-length COP1

et al. 2007

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Human promyelocytic leukemia protein is targeted to distinct subnuclear domains in plant nuclei and colocalizes with nucleolar constituents in a SUMO‐dependent manner

et al. 2016

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Eukaryotic nuclei are subdivided into subnuclear structures. Among the most prominent of these structures are the nucleolus and the PML nuclear bodies (PML‐NBs). PML‐NBs are spherical multiprotein aggregates of varying size localized in the interchromosomal area. PML‐NB formation is dependent on the presence of the promyelocytic leukemia protein (PML) as well as on post‐translational modification of core components by covalent attachment of the small ubiquitin‐like modifier (SUMO). So far, PML‐NBs as well as PML have been described in mammalian cells only, whereas no orthologs are known in the plant kingdom. In order to investigate conserved mechanisms in PML targeting, we expressed human PML (hPML) fused to the GFP in Nicotiana benthamiana. Using confocal laser scanning microscopy and coimmunoprecipitation followed by mass spectrometric analysis, we found the fusion protein in association with nucleolar constituents. Importantly, mutants of hPML, which are no longer SUMOylated, showed altered localizations, implying SUMO‐dependent targeting of hPML in plants as has previously been shown for mammalian cells. Interestingly, in the presence of proteasome inhibitors, hPML could also be found in the nucleolus of mammalian cells suggesting conserved targeting mechanisms of PML across kingdoms. Finally, Solanum tuberosum COP1, a proposed PML‐like protein from plants, was fused to the red fluorescent protein (RFP) and coexpressed with hPML::eGFP. Microscopic analysis confirmed the localization of COP1::RFP in nuclear speckles. However, hPML::eGFP did not colocalize with COP1::RFP. Hence, we conclude that plants do not possess specialized PML‐NBs, but that their functions may be covered by other subnuclear structures like the nucleolus. Database Proteomics data have been deposited to the ProteomeXchange Consortium with the identifier PXD004254.

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ThePCIComplexes and the Ubiquitin Proteasome System (UPS) in Plant Development

Halimi

Chamovitz

2018

Annual Plant Reviews Online

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Since the discovery of the ubiquitin proteasome system (UPS) in the 1970s, the UPS field has advanced remarkably, culminating in the 2004 Nobel Prize in Chemistry. The idea that energy should be invested to degrade a substrate, whose own synthesis consumed energy in the first place, was revolutionary (Hershko and Tomkins, 1971). InArabidopsis, ~1400 genes encode components of the UPS, constituting approximately 5% of theArabidopsisproteome (Smalle and Vierstra, 2004), eluding to the great complexity of the UPS system. Describing this complexity is daunting and very much a matter of perspective. This chapter will discuss the UPS in plant development from the point of view of the PCI (Proteasome,CSN, eIF3) or “ZOMES” complexes: the 26S proteasome lid, Cop9 signalosome (CSN), and eIF3 (eukaryote initiation factor 3), and in particular from the point of view of the CSN.

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Characterization of Human Constitutive Photomorphogenesis Protein 1, a RING Finger Ubiquitin Ligase That Interacts with Jun Transcription Factors and Modulates Their Transcriptional Activity

Cited by 96 publications

References 53 publications

COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1) product, stabilizes UV stress-induced c-Jun through inhibition of full-length COP1

COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1) product, stabilizes UV stress-induced c-Jun through inhibition of full-length COP1

Human promyelocytic leukemia protein is targeted to distinct subnuclear domains in plant nuclei and colocalizes with nucleolar constituents in a SUMO‐dependent manner

ThePCIComplexes and the Ubiquitin Proteasome System (UPS) in Plant Development

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