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Heike Laman - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the FBXO7 promoter reveals overlapping Pax5 and c-Myb binding sites functioning in B cells.
Biochemical and biophysical research communications, 2021Co-Authors: Rebecca B. Harris, Suzanne J. Randle, Heike LamanAbstract:Abstract FBXO7 is a key player in the differentiation and function of numerous blood cell types, and in neurons, oligodendrocytes and spermatocytes. In an effort to gain insight into the physiological and pathological settings where FBXO7 is likely to play a key role, we sought to define the transcription factors which direct FBXO7 expression. Using sequence alignments across 28 species, we defined the human FBXO7 promoter and found that it contains two conserved regions enriched for multiple transcription factor binding sites. Many of these have roles in either neuronal or haematopoietic development. Using various FBXO7 promoter reporters, we found ELF4, Pax5 and c-Myb have functional binding sites that activate transcription. We find endogenous Pax5 is bound to the FBXO7 promoter in pre-B cells, and that the exogenous expression of Pax5 represses FBXO7 transcription in early pro-B cells.
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Analysis of the FBXO7 promoter reveals overlapping Pax5 and c-Myb binding sites functioning in B cells
2019Co-Authors: Suzanne J. Randle, Heike LamanAbstract:Abstract FBXO7 is a key player in the differentiation and function of numerous blood cell types, and in neurons, oligodendrocytes and spermatocytes. In an effort to gain insight into the physiological and pathological settings where FBXO7 is likely to play a key role, we sought to define the transcription factors which direct FBXO7 expression. Using sequence alignments across 28 species, we defined the human FBXO7 promoter and found that it contains two conserved regions enriched for multiple transcription factor binding sites. Many of these have roles in either neuronal or haematopoietic development. Using various FBXO7 promoter reporters, we found ELF4, Pax5 and c-Myb have functional binding sites that activate transcription. Overlap of Pax5 and c-Myb binding sites suggest that these factors bind cooperatively to transactivate the FBXO7 promoter. Although endogenous Pax5 is bound to the FBXO7 promoter in B cells, c-Myb is also required for FBXO7 expression. Our data suggest the interplay of multiple transcription factors regulate the FBXO7 promoter.
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Loss of FBXO7 results in a Parkinson's-like dopaminergic degeneration via an RPL23-MDM2-TP53 pathway.
The Journal of pathology, 2019Co-Authors: Simon R.w. Stott, Suzanne J. Randle, Rebecca B. Harris, Sara Al Rawi, Paulina A Rowicka, Bethany Mason, Jing Xia, Jeffrey W. Dalley, Roger A. Barker, Heike LamanAbstract:The field of Parkinson's disease research has been impeded by the absence of animal models that clearly phenocopy the features of this neurodegenerative condition. Mutations in FBXO7/PARK15 are associated with both sporadic Parkinson's disease and a severe form of autosomal recessive early-onset Parkinsonism. Here we report that conditional deletion of FBXO7 in the midbrain dopamine neurons results in an early reduction in striatal dopamine levels, together with a slow, progressive loss of midbrain dopamine neurons and onset of locomotor defects. Unexpectedly, a later compensatory response led to a near-full restoration of dopaminergic fibre innervation in the striatum, but nigral cell loss was irreversible. Mechanistically, there was increased expression in the dopamine neurons of FBXO7-interacting protein, RPL23, which is a sensor of ribosomal stress that inhibits MDM2, the negative regulator of p53. A corresponding activated p53 transcriptional signature biased towards pro-apoptotic genes was also observed. These data suggest that the neuroprotective role of FBXO7 involves its suppression of the RPL23-MDM2-p53 axis that promotes cell death in dopaminergic midbrain neurons. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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A conserved requirement for FBXO7 during male germ cell cytoplasmic remodelling
2019Co-Authors: Claudia Cattoni Rathje, Suzanne J. Randle, Sara Al Rawi, Benjamin M. Skinner, Emma Elizabeth Philippa Johnson, Joanne Bacon, Myrto Vlazaki, Nabeel A. Affara, Peter J.i. Ellis, Heike LamanAbstract:Summary statement FBXO7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here we show that in addition to the previously-known Parkinsonian and haematopoietic phenotypes, FBXO7-deficient male mice are completely sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the cells undergo cytoplasmic remodelling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in FBXO7-deficient males. Mutation of the Drosophila FBXO7 orthologue, nutcracker (ntc) was previously shown to cause sterility at a similar stage of germ cell development, indicating that the requirement for FBXO7 is conserved. The ntc phenotype was attributed to proteasome mis-regulation via an interaction with the proteasome regulator, DmPI31. Our data suggest rather that in mice, the requirement for FBXO7 is either independent of its interaction with PI31, or relates specifically to cytoplasmic proteasome activity during spermiogenesis.
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structure and function of FBXO7 park15 in parkinson s disease
Current Protein & Peptide Science, 2017Co-Authors: Suzanne J. Randle, Heike LamanAbstract:FBXO7/PARK15 has well-defined roles, acting as part of a Skp1-Cul1-F box protein (SCF)- type E3 ubiquitin ligase and also having SCF-independent activities. Mutations within FBXO7 have been found to cause an early-onset Parkinson's disease, and these are found within or near to its functional domains, including its F-box domain (FBD), its proline rich region (PRR), and its ubiquitinlike domain (Ubl). We highlight recent advances in our understanding of FBXO7 function in Parkinson's disease, with respect to these mutations and where they occur in the FBXO7 protein. We hypothesize that many of FBXO7 functions contribute to its role in PD pathogenesis.
Suzanne J. Randle - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the FBXO7 promoter reveals overlapping Pax5 and c-Myb binding sites functioning in B cells.
Biochemical and biophysical research communications, 2021Co-Authors: Rebecca B. Harris, Suzanne J. Randle, Heike LamanAbstract:Abstract FBXO7 is a key player in the differentiation and function of numerous blood cell types, and in neurons, oligodendrocytes and spermatocytes. In an effort to gain insight into the physiological and pathological settings where FBXO7 is likely to play a key role, we sought to define the transcription factors which direct FBXO7 expression. Using sequence alignments across 28 species, we defined the human FBXO7 promoter and found that it contains two conserved regions enriched for multiple transcription factor binding sites. Many of these have roles in either neuronal or haematopoietic development. Using various FBXO7 promoter reporters, we found ELF4, Pax5 and c-Myb have functional binding sites that activate transcription. We find endogenous Pax5 is bound to the FBXO7 promoter in pre-B cells, and that the exogenous expression of Pax5 represses FBXO7 transcription in early pro-B cells.
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The E3 ubiquitin ligase SCF(FBXO7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway.
Biochimica et biophysica acta. General subjects, 2020Co-Authors: Valentine Spagnol, Tycho Et Mevissen, Suzanne J. Randle, Caio Almeida Batista De ,oliveira, Patrícia Maria Siqueira Dos Passos, Camila R S T B De Correia, Natália Borges Simaroli, Joice S. Oliveira, A.c. Medeiros, Marcelo D. GomesAbstract:Abstract Background Ubiquitously eXpressed Transcript isoform 2 (UXT V2) is a prefoldin-like protein involved in NF-κB signaling, apoptosis, and the androgen and estrogen response. UXT-V2 is a cofactor in the NF-κB transcriptional enhanceosome, and its knockdown inhibits TNF-α -induced NF-κB activation. FBXO7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(FBXO7) E3 ubiquitin ligase complex. FBXO7 negatively regulates NF-κB signaling through TRAF2 and cIAP1 ubiquitination. Methods We combine co-immunoprecipitation, ubiquitination in vitro and in vivo, cycloheximide chase assay, ubiquitin chain restriction analysis and microscopy to investigate interaction between FBXO7 and overexpressed UXT-V2-HA. Results The Ubl domain of FBXO7 contributes to interaction with UXT V2. This substrate is polyubiquitinated by SCF(FBXO7) with K48 and K63 ubiquitin chain linkages in vitro and in vivo. This post-translational modification decreases UXT-V2 stability and promotes its proteasomal degradation. We further show that UXT V1, an alternatively spliced isoform of UXT, containing 12 additional amino acids at the N-terminus as compared to UXT V2, also interacts with and is ubiquitinated by FBXO7. Moreover, FBXO7 knockdown promotes UXT-V2 accumulation, and the overexpression of FBXO7-ΔF-box protects UXT-V2 from proteasomal degradation and enhances the responsiveness of NF-κB reporter. We find that UXT-V2 colocalizes with FBXO7 in the cell nucleus. Conclusions Together, our study reveals that SCF(FBXO7) mediates the proteasomal degradation of UXT-V2 causing the inhibition of the NF-κB signaling pathway. General significance Discovering new substrates of E3 ubiquitin-ligase SCF(FBXO7) contributes to understand its function in different diseases such as cancer and Parkinson.
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Analysis of the FBXO7 promoter reveals overlapping Pax5 and c-Myb binding sites functioning in B cells
2019Co-Authors: Suzanne J. Randle, Heike LamanAbstract:Abstract FBXO7 is a key player in the differentiation and function of numerous blood cell types, and in neurons, oligodendrocytes and spermatocytes. In an effort to gain insight into the physiological and pathological settings where FBXO7 is likely to play a key role, we sought to define the transcription factors which direct FBXO7 expression. Using sequence alignments across 28 species, we defined the human FBXO7 promoter and found that it contains two conserved regions enriched for multiple transcription factor binding sites. Many of these have roles in either neuronal or haematopoietic development. Using various FBXO7 promoter reporters, we found ELF4, Pax5 and c-Myb have functional binding sites that activate transcription. Overlap of Pax5 and c-Myb binding sites suggest that these factors bind cooperatively to transactivate the FBXO7 promoter. Although endogenous Pax5 is bound to the FBXO7 promoter in B cells, c-Myb is also required for FBXO7 expression. Our data suggest the interplay of multiple transcription factors regulate the FBXO7 promoter.
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Loss of FBXO7 results in a Parkinson's-like dopaminergic degeneration via an RPL23-MDM2-TP53 pathway.
The Journal of pathology, 2019Co-Authors: Simon R.w. Stott, Suzanne J. Randle, Rebecca B. Harris, Sara Al Rawi, Paulina A Rowicka, Bethany Mason, Jing Xia, Jeffrey W. Dalley, Roger A. Barker, Heike LamanAbstract:The field of Parkinson's disease research has been impeded by the absence of animal models that clearly phenocopy the features of this neurodegenerative condition. Mutations in FBXO7/PARK15 are associated with both sporadic Parkinson's disease and a severe form of autosomal recessive early-onset Parkinsonism. Here we report that conditional deletion of FBXO7 in the midbrain dopamine neurons results in an early reduction in striatal dopamine levels, together with a slow, progressive loss of midbrain dopamine neurons and onset of locomotor defects. Unexpectedly, a later compensatory response led to a near-full restoration of dopaminergic fibre innervation in the striatum, but nigral cell loss was irreversible. Mechanistically, there was increased expression in the dopamine neurons of FBXO7-interacting protein, RPL23, which is a sensor of ribosomal stress that inhibits MDM2, the negative regulator of p53. A corresponding activated p53 transcriptional signature biased towards pro-apoptotic genes was also observed. These data suggest that the neuroprotective role of FBXO7 involves its suppression of the RPL23-MDM2-p53 axis that promotes cell death in dopaminergic midbrain neurons. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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A conserved requirement for FBXO7 during male germ cell cytoplasmic remodelling
2019Co-Authors: Claudia Cattoni Rathje, Suzanne J. Randle, Sara Al Rawi, Benjamin M. Skinner, Emma Elizabeth Philippa Johnson, Joanne Bacon, Myrto Vlazaki, Nabeel A. Affara, Peter J.i. Ellis, Heike LamanAbstract:Summary statement FBXO7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here we show that in addition to the previously-known Parkinsonian and haematopoietic phenotypes, FBXO7-deficient male mice are completely sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the cells undergo cytoplasmic remodelling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in FBXO7-deficient males. Mutation of the Drosophila FBXO7 orthologue, nutcracker (ntc) was previously shown to cause sterility at a similar stage of germ cell development, indicating that the requirement for FBXO7 is conserved. The ntc phenotype was attributed to proteasome mis-regulation via an interaction with the proteasome regulator, DmPI31. Our data suggest rather that in mice, the requirement for FBXO7 is either independent of its interaction with PI31, or relates specifically to cytoplasmic proteasome activity during spermiogenesis.
Marcelo D. Gomes - One of the best experts on this subject based on the ideXlab platform.
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The E3 ubiquitin ligase SCF(FBXO7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway.
Biochimica et biophysica acta. General subjects, 2020Co-Authors: Valentine Spagnol, Tycho Et Mevissen, Suzanne J. Randle, Caio Almeida Batista De ,oliveira, Patrícia Maria Siqueira Dos Passos, Camila R S T B De Correia, Natália Borges Simaroli, Joice S. Oliveira, A.c. Medeiros, Marcelo D. GomesAbstract:Abstract Background Ubiquitously eXpressed Transcript isoform 2 (UXT V2) is a prefoldin-like protein involved in NF-κB signaling, apoptosis, and the androgen and estrogen response. UXT-V2 is a cofactor in the NF-κB transcriptional enhanceosome, and its knockdown inhibits TNF-α -induced NF-κB activation. FBXO7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(FBXO7) E3 ubiquitin ligase complex. FBXO7 negatively regulates NF-κB signaling through TRAF2 and cIAP1 ubiquitination. Methods We combine co-immunoprecipitation, ubiquitination in vitro and in vivo, cycloheximide chase assay, ubiquitin chain restriction analysis and microscopy to investigate interaction between FBXO7 and overexpressed UXT-V2-HA. Results The Ubl domain of FBXO7 contributes to interaction with UXT V2. This substrate is polyubiquitinated by SCF(FBXO7) with K48 and K63 ubiquitin chain linkages in vitro and in vivo. This post-translational modification decreases UXT-V2 stability and promotes its proteasomal degradation. We further show that UXT V1, an alternatively spliced isoform of UXT, containing 12 additional amino acids at the N-terminus as compared to UXT V2, also interacts with and is ubiquitinated by FBXO7. Moreover, FBXO7 knockdown promotes UXT-V2 accumulation, and the overexpression of FBXO7-ΔF-box protects UXT-V2 from proteasomal degradation and enhances the responsiveness of NF-κB reporter. We find that UXT-V2 colocalizes with FBXO7 in the cell nucleus. Conclusions Together, our study reveals that SCF(FBXO7) mediates the proteasomal degradation of UXT-V2 causing the inhibition of the NF-κB signaling pathway. General significance Discovering new substrates of E3 ubiquitin-ligase SCF(FBXO7) contributes to understand its function in different diseases such as cancer and Parkinson.
Tycho Et Mevissen - One of the best experts on this subject based on the ideXlab platform.
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The E3 ubiquitin ligase SCF(FBXO7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway.
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Spagnol Valentine, Caio Ab Oliveira, Randle, Suzanne J, Patrícia Ms Passos, Correia, Camila Rstb, Simaroli, Natália B, Oliveira, Joice S, Tycho Et Mevissen, Medeiros, Ana Carla, Gomes, Marcelo DAbstract:Ubiquitously eXpressed Transcript isoform 2 (UXT-V2) is a prefoldin-like protein involved in NF-kappa B signaling, apoptosis, and the androgen and estrogen response. UXT-V2 is a cofactor in the NF-κB transcriptional enhanceosome, and its knockdown inhibits TNF-alpha-induced NF-kappa B activation. FBXO7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(FBXO7) E3 ubiquitin ligase complex. FBXO7 negatively regulates NF-kappa B signaling through TRAF2 and cIAP1 ubiquitination.Biotechnology and Biological Science Research Council [BB/J007846/1]
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The E3 ubiquitin ligase SCF(FBXO7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway.
Biochimica et biophysica acta. General subjects, 2020Co-Authors: Valentine Spagnol, Tycho Et Mevissen, Suzanne J. Randle, Caio Almeida Batista De ,oliveira, Patrícia Maria Siqueira Dos Passos, Camila R S T B De Correia, Natália Borges Simaroli, Joice S. Oliveira, A.c. Medeiros, Marcelo D. GomesAbstract:Abstract Background Ubiquitously eXpressed Transcript isoform 2 (UXT V2) is a prefoldin-like protein involved in NF-κB signaling, apoptosis, and the androgen and estrogen response. UXT-V2 is a cofactor in the NF-κB transcriptional enhanceosome, and its knockdown inhibits TNF-α -induced NF-κB activation. FBXO7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(FBXO7) E3 ubiquitin ligase complex. FBXO7 negatively regulates NF-κB signaling through TRAF2 and cIAP1 ubiquitination. Methods We combine co-immunoprecipitation, ubiquitination in vitro and in vivo, cycloheximide chase assay, ubiquitin chain restriction analysis and microscopy to investigate interaction between FBXO7 and overexpressed UXT-V2-HA. Results The Ubl domain of FBXO7 contributes to interaction with UXT V2. This substrate is polyubiquitinated by SCF(FBXO7) with K48 and K63 ubiquitin chain linkages in vitro and in vivo. This post-translational modification decreases UXT-V2 stability and promotes its proteasomal degradation. We further show that UXT V1, an alternatively spliced isoform of UXT, containing 12 additional amino acids at the N-terminus as compared to UXT V2, also interacts with and is ubiquitinated by FBXO7. Moreover, FBXO7 knockdown promotes UXT-V2 accumulation, and the overexpression of FBXO7-ΔF-box protects UXT-V2 from proteasomal degradation and enhances the responsiveness of NF-κB reporter. We find that UXT-V2 colocalizes with FBXO7 in the cell nucleus. Conclusions Together, our study reveals that SCF(FBXO7) mediates the proteasomal degradation of UXT-V2 causing the inhibition of the NF-κB signaling pathway. General significance Discovering new substrates of E3 ubiquitin-ligase SCF(FBXO7) contributes to understand its function in different diseases such as cancer and Parkinson.
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Gsk3β and Tomm20 are substrates of the SCFFBXO7/PARK15 ubiquitin ligase associated with Parkinson's disease.
The Biochemical journal, 2016Co-Authors: Felipe R. Teixeira, Tycho Et Mevissen, Suzanne J. Randle, Shachi P. Patel, Grasilda Zenkeviciute, Tie Koide, David Komander, Heike LamanAbstract:FBXO7 is a clinically relevant F-box protein, associated with both cancer and Parkinson's disease (PD). Additionally, SNPs within FBXO7 are correlated with alterations in red blood cell parameters. Point mutations within FBXO7 map within specific functional domains, including near its F-box domain and its substrate recruiting domains, suggesting that deficiencies in SCFFBXO7/PARK15 ubiquitin ligase activity are mechanistically linked to early-onset PD. To date, relatively few substrates of the ligase have been identified. These include HURP (hepatoma up-regulated protein), whose ubiquitination results in proteasome-mediated degradation, and c-IAP1 (inhibitor of apoptosis protein 1), TNF receptor-associated factor 2 (TRAF2), and NRAGE, which are not destabilized as a result of ubiquitination. None of these substrates have been linked directly to PD, nor has it been determined whether they would directly engage neuronal cell death pathways. To discover ubiquitinated substrates of SCFFBXO7 implicated more directly in PD aetiology, we conducted a high-throughput screen using protein arrays to identify new candidates. A total of 338 new targets were identified and from these we validated glycogen synthase kinase 3β (Gsk3β), which can phosphorylate α-synuclein, and translocase of outer mitochondrial membrane 20 (Tomm20), a mitochondrial translocase that, when ubiquitinated, promotes mitophagy, as SCFFBXO7 substrates both in vitro and in vivo Ubiquitin chain restriction analyses revealed that FBXO7 modified Gsk3β using K63 linkages. Our results indicate that FBXO7 negatively regulates Gsk3β activity, rather than its levels or localization. In addition, FBXO7 ubiquitinated Tomm20, and its levels correlated with FBXO7 expression, indicating a stabilizing effect. None of the PD-associated mutations in FBXO7 impaired Tomm20 ubiquitination. Our findings demonstrate that SCFFBXO7 has an impact directly on two proteins implicated in pathological processes leading to PD.
Valentine Spagnol - One of the best experts on this subject based on the ideXlab platform.
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The E3 ubiquitin ligase SCF(FBXO7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway.
Biochimica et biophysica acta. General subjects, 2020Co-Authors: Valentine Spagnol, Tycho Et Mevissen, Suzanne J. Randle, Caio Almeida Batista De ,oliveira, Patrícia Maria Siqueira Dos Passos, Camila R S T B De Correia, Natália Borges Simaroli, Joice S. Oliveira, A.c. Medeiros, Marcelo D. GomesAbstract:Abstract Background Ubiquitously eXpressed Transcript isoform 2 (UXT V2) is a prefoldin-like protein involved in NF-κB signaling, apoptosis, and the androgen and estrogen response. UXT-V2 is a cofactor in the NF-κB transcriptional enhanceosome, and its knockdown inhibits TNF-α -induced NF-κB activation. FBXO7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(FBXO7) E3 ubiquitin ligase complex. FBXO7 negatively regulates NF-κB signaling through TRAF2 and cIAP1 ubiquitination. Methods We combine co-immunoprecipitation, ubiquitination in vitro and in vivo, cycloheximide chase assay, ubiquitin chain restriction analysis and microscopy to investigate interaction between FBXO7 and overexpressed UXT-V2-HA. Results The Ubl domain of FBXO7 contributes to interaction with UXT V2. This substrate is polyubiquitinated by SCF(FBXO7) with K48 and K63 ubiquitin chain linkages in vitro and in vivo. This post-translational modification decreases UXT-V2 stability and promotes its proteasomal degradation. We further show that UXT V1, an alternatively spliced isoform of UXT, containing 12 additional amino acids at the N-terminus as compared to UXT V2, also interacts with and is ubiquitinated by FBXO7. Moreover, FBXO7 knockdown promotes UXT-V2 accumulation, and the overexpression of FBXO7-ΔF-box protects UXT-V2 from proteasomal degradation and enhances the responsiveness of NF-κB reporter. We find that UXT-V2 colocalizes with FBXO7 in the cell nucleus. Conclusions Together, our study reveals that SCF(FBXO7) mediates the proteasomal degradation of UXT-V2 causing the inhibition of the NF-κB signaling pathway. General significance Discovering new substrates of E3 ubiquitin-ligase SCF(FBXO7) contributes to understand its function in different diseases such as cancer and Parkinson.
