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Query: UNIPROT:P06889 (Mol)
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The vascular wilt pathogen Fusarium oxysporum f. sp. lycopersici efficiently invades roots and colonizes vascular tissues of its host tomato. For these processes, the F-box protein Frp1 is required. The Fusarium oxysporum Deltafrp1 mutant was characterized in detail to uncover the cause of its colonization defect. Using growth assays, we could attribute poor root colonization to reduced assimilation of organic acids, amino acids (except proline), or polysaccharides, singly or in combination. External root colonization by the Deltafrp1 mutant is restored by the addition of 0.1% glucose or proline but infection still does not occur. This is due to the inability of the Deltafrp1 mutant to penetrate the roots, as demonstrated by the lack of expression of SIX1 in the Deltafrp1 strain, which is a gene exclusively expressed inside roots, and loss of cell wall-degrading enzyme (CWDE) gene expression. Many of the metabolic defects of the Deltafrp1 strain can be attributed to reduced expression of the ICL1 (isocitrate lyase) gene. Strikingly, an Deltaicl1 mutant is still fully pathogenic and capable of external root colonization. We conclude that the inability of the Deltafrp1 strain to colonize and invade roots is not primarily due to metabolic defects but can be attributed to reduced expression of several CWDE genes.
Mol Plant Microbe Interact 2009 May
PMID:Impaired colonization and infection of tomato roots by the Deltafrp1 mutant of Fusarium oxysporum correlates with reduced CWDE gene expression. 1934 69

Mdm30p, a nucleus-encoded F-box protein, which binds to the substrate for ubiquitin-mediated proteolysis, is involved in maintenance of fusion-competent mitochondria for various cellular functions. Recently, Mdm30p has been implicated in regulation of gene expression. However, its mode of action in gene regulation is not clearly known in vivo. With this view, we have systematically analyzed here the role of Mdm30p in regulation of transcriptional initiation, elongation, mRNA processing, and export in Saccharomyces cerevisiae, using a formaldehyde-based in vivo cross-linking and chromatin immunoprecipitation assay in conjunction with RT-PCR and fluorescence in situ hybridization. We show that Mdm30p is dispensable for formation of the preinitiation complex assembly, association of elongating RNA polymerase II, and recruitment of mRNA capping enzyme, cap-binding complex, and 3' end formation machinery at the transcriptionally active genes such as ADH1, PHO84, and RPS5. Intriguingly, we find that Mdm30p facilitates the recruitment of the transcription-export complex at these genes. Consistently, the export of mRNAs of these genes is significantly impaired in the absence of Mdm30p as revealed by fluorescence in situ hybridization and RT-PCR analysis of cytoplasmic mRNA. However, such an impaired mRNA export is not dependent on mitochondrial fusion, as the deletion of FZO1, an essential gene for mitochondrial fusion, does not alter the export of ADH1, PHO84, and RPS5 mRNAs. Together, our data demonstrate that Mdm30p selectively controls mRNA export independently of mitochondrial fusion, revealing a novel function of an F-box protein in mRNA export.
J Mol Biol 2009 Jun 05
PMID:Stimulation of mRNA export by an F-box protein, Mdm30p, in vivo. 1937 28

Fbxo45 is an F-box protein that is restricted to the nervous system. Unlike other F-box proteins, Fbxo45 was found not to form an SCF complex as a result of an amino acid substitution in the consensus sequence for Cul1 binding. Proteomics analysis revealed that Fbxo45 specifically associates with PAM (protein associated with Myc), a RING finger-type ubiquitin ligase. Mice deficient in Fbxo45 were generated and found to die soon after birth as a result of respiratory distress. Fbxo45(-)(/)(-) embryos show abnormal innervation of the diaphragm, impaired synapse formation at neuromuscular junctions, and aberrant development of axon fiber tracts in the brain. Similar defects are also observed in mice lacking Phr1 (mouse ortholog of PAM), suggesting that Fbxo45 and Phr1 function in the same pathway. In addition, neuronal migration was impaired in Fbxo45(-)(/)(-) mice. These results suggest that Fbxo45 forms a novel Fbxo45-PAM ubiquitin ligase complex that plays an important role in neural development.
Mol Cell Biol 2009 Jul
PMID:Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development. 1939 81

F-box protein family is characterized by an F-box motif that has been shown to be critical for the controlled degradation of regulatory proteins. In plant, F-box protein plays an important role in signal pathways and involved in various signal transduction systems. A full-length cDNA encoding a putative F-box protein, designated as BnSLY1, was isolated from Brassica napus. The full-length cDNA of BnSLY1 was 809 bp containing a 438 bp open reading frame encoding a precursor protein of 138 amino acid residues. Comparative and bioinformatic analyses revealed that BnSLY1 showed high degree of homology with F-box proteins from other plant species and contained F-box, GGF and LSL conserved motifs. The expression of BnSLY1 under exogenous gibberellins acid-3 (GA3), abscisic acid (ABA) and GA biosynthetic inhibitor paclobutrazol (PAC) was analyzed using real-time PCR. The results showed that the expression of BnSLY1 was down-regulated after GA3 treatment and prominently induced by ABA in the low concentrations. Moreover, BnSLY1 was also induction in the high concentrations of PAC. These results suggest that the expression of BnSLY1 was regulated by the exogenous GA3, ABA and PAC and may be related to endogenous level of GA in B. napus.
Mol Biol Rep 2010 Feb
PMID:Molecular cloning and expression analysis of an F-box protein gene responsive to plant hormones in Brassica napus. 1975 59

Cul3, a Cullin family scaffold protein, is thought to mediate the assembly of a large number of SCF (Skp1-Cullin1-F-box protein)-like ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors. Cul3 controls early embryonic development in several genetic models through mechanisms not understood. Very few functional substrate/adaptor pairs for Cul3 ubiquitin ligases have been identified. Here, we show that Cul3 knockdown in human cells results in abnormal actin stress fibers and distorted cell morphology, owing to impaired ubiquitination and degradation of small GTPase RhoA. We identify a family of RhoA-binding BTB domain adaptors conserved from insects to mammals, designated BACURDs. BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Dysfunction of the Cul3/BACURD complex decreases cell migration potential and impairs RhoA-mediated convergent extension movements during Xenopus gastrulation. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.
Mol Cell 2009 Sep 24
PMID:Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. 1978 22

PHLPP1 belongs to a novel family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt signaling. Our recent studies have demonstrated that loss of PHLPP expression occurs at high frequency in colorectal cancer. In this study, we identified PHLPP1 as a proteolytic target of a beta-TrCP-containing Skp-Cullin 1-F-box protein (SCF) complex (SCF(beta-TrCP)) E3 ubiquitin ligase in a phosphorylation-dependent manner. Overexpression of wild-type but not DeltaF-box mutant beta-TrCP leads to decreased expression and increased ubiquitination of PHLPP1, whereas knockdown of endogenous beta-TrCP has the opposite effect. In addition, we show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity. Furthermore, expression of a degradation-deficient PHLPP1 mutant in colon cancer cells results in a more effective dephosphorylation of Akt and inhibition of cell growth. Taken together, our findings demonstrate a key role for beta-TrCP in controlling the level of PHLPP1, and activation of Akt negatively regulates this degradation process.
Mol Cell Biol 2009 Dec
PMID:beta-TrCP-mediated ubiquitination and degradation of PHLPP1 are negatively regulated by Akt. 1979 85

A stable genome is critical to cell viability and proliferation. During DNA replication, the S-phase checkpoint pathway responds to replication stress. In budding yeast, the chromatin-bound F-box protein Dia2 is required to maintain genomic stability and may help replication complexes overcome sites of damaged DNA and natural fragile regions. SCF (Skp1/Cul1/F-box protein) complexes are modular ubiquitin ligases. We show here that Dia2 is itself targeted for ubiquitin-mediated proteolysis and that activation of the S-phase checkpoint pathway inhibits Dia2 protein degradation. S-phase checkpoint mutants fail to stabilize Dia2 in response to replication stress. Deletion of DIA2 from these checkpoint mutants exacerbates their sensitivity to hydroxyurea, suggesting that stabilization of Dia2 contributes to the replication stress response. Unlike the case for other F-box proteins, deletion of the F-box domain in Dia2 does not stabilize the protein. Rather, an N-terminal domain that is also required for nuclear localization is necessary for degradation. When a strong nuclear localization signal (NLS) is added to dia2 mutants lacking this domain, the Dia2 protein is both stable and nuclear. Together, our results suggest that Dia2 protein turnover does not involve an autocatalytic mechanism and that Dia2 proteolysis is inhibited by activation of the replication stress response.
Mol Cell Biol 2010 Jan
PMID:Activation of the S-phase checkpoint inhibits degradation of the F-box protein Dia2. 1985 92

The F-box protein Frp1 is required for pathogenicity of Fusarium oxysporum f. sp. lycopersici towards tomato. The Delta frp1 mutant is deficient in expression of genes for cell wall-degrading enzymes (CWDEs) and ICL1, encoding a key enzyme for the assimilation of C2 carbon sources. An explanation for the inability of the Delta frp1 mutant to express these genes may be found in constitutive carbon catabolite repression. Cre1 is the transcriptional repressor in filamentous fungi known to repress several CWDE genes and other genes required for assimilation of non-sugar carbon sources. Here, we demonstrate that Frp1 and Cre1 both control the repression/derepression state of such genes. The replacement of CRE1 with GST::CRE1 resulted in a derepressed phenotype in wild-type background, suggesting that this replacement affects Cre1 function. Strikingly, in the Delta frp1 mutant the replacement of CRE1 with GST::CRE1 restored pathogenicity, growth on ethanol and expression of ICL1 and CWDE genes. A GFP-Cre1 fusion protein is not degraded nor exported out of the nucleus during growth on ethanol, a derepressing carbon source, suggesting that Cre1 is not likely a target of Frp1 for degradation by the proteasome. We conclude that both proteins function together to regulate transcription of carbon source utilization genes.
Mol Microbiol 2009 Dec
PMID:Mutation of CRE1 in Fusarium oxysporum reverts the pathogenicity defects of the FRP1 deletion mutant. 1991 43

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein beta-transducin repeat-containing protein (beta-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans beta-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant.
Mol Biol Cell 2010 Mar 01
PMID:Fate specification and tissue-specific cell cycle control of the Caenorhabditis elegans intestine. 2005 85

The universal cyclin-dependent kinase inhibitor p27(Kip1) functions as a tumor suppressor, and reduced levels of p27(Kip1) connote poor prognosis in several human malignancies. p27(Kip1) levels are predominately regulated by ubiquitin-mediated turnover of the protein, which is marked for destruction by the E3 ubiquitin ligase SCF(Skp2) complex following its phosphorylation by the cyclin E-cyclin-dependent kinase 2 complex. Binding of phospho-p27(Kip1) is directed by the Skp2 F-box protein, and this is greatly augmented by its allosteric regulator Cks1. We have established that programmed expression of c-Myc in the B cells of Emu-Myc transgenic mice triggers p27(Kip1) destruction by inducing Cks1, that this response controls Myc-driven proliferation, and that loss of Cks1 markedly delays Myc-induced lymphomagenesis and cancels the dissemination of these tumors. Here, we report that elevated levels of Skp2 are a characteristic of Emu-Myc lymphomas and of human Burkitt lymphoma that bear MYC/Immunoglobulin chromosomal translocations. As expected, Myc-mediated suppression of p27(Kip1) was abolished in Skp2-null Emu-Myc B cells. However, the effect of Skp2 loss on Myc-driven proliferation and lymphomagenesis was surprisingly modest compared with the effects of Cks1 loss. Collectively, these findings suggest that Cks1 targets, in addition to p27(Kip1), are critical for Myc-driven proliferation and tumorigenesis.
Mol Cancer Res 2010 Mar
PMID:Skp2 directs Myc-mediated suppression of p27Kip1 yet has modest effects on Myc-driven lymphomagenesis. 2019 82


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