Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As the largest class of disease resistance R genes, the genes encoding nucleotide binding site and leucine-rich repeat proteins ("NBS-LRR genes") play a critical role in defending plants from a multitude of pathogens and pests. The diversity of NBS-LRR genes was examined in the Populus trichocarpa draft genome sequence. The NBS class of genes in this perennial tree is large and diverse, comprised of approximately 400 genes, at least twice the complement of Arabidopsis. The NBS family can be divided into multiple subfamilies with distinct domain organizations. It includes 119 Coiled-Coil-NBS-LRR genes, 64 TIR-NBS-LRR genes, 34 BED-finger-NBS-LRR, and both truncated and unusual NBS- and NBS-LRR-containing genes. The transcripts of only 34 NBS-LRR genes were detected in rust-infected and non-infected leaves using a whole-genome oligoarray. None showed an altered expression two days post inoculation.
Plant Mol Biol 2008 Apr
PMID:Genome-wide identification of NBS resistance genes in Populus trichocarpa. 1824 36

Class IA phosphoinositide 3-kinases (PI 3-kinases) are key signaling components downstream of tyrosine kinases and Ras, regulating many different cellular functions and contributing to tumorigenesis. Class IA PI 3-kinases are heterodimers comprised of a p85 regulatory and a p110 catalytic subunit. Nijmegen breakage syndrome (NBS) is a chromosomal instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product p95 (also known as NBS1) is part of the Mre11-Rad50-Nbs1 complex, a central player associated with double-strand break repair. We previously demonstrated that NBS1 overexpression induces transformation through activation of PI 3-kinase/Akt. In this study, we show that NBS1 directly interacts, through a highly conserved C-terminal motif (aa 653-669) of NBS1, with the N-terminal domain (aa 1-108) of the p110alpha catalytic subunit of PI 3-kinase, and stimulates PI 3-kinase activity. Mutations of different regions of the conserved motif abolish the ability of NBS1 to activate PI 3-kinase in vitro and in vivo. Co-expression of NBS1/p110alpha/p-Akt is observed in certain percentage of head and neck cancer patient samples. These results demonstrate that NBS1 can function as an adaptor/activator of p110alpha PI 3-kinase through a novel activation motif, consistent with its possible role in cell transformation and tumorigenesis.
J Mol Med (Berl) 2008 Apr
PMID:Activation of phosphoinositide 3-kinase by the NBS1 DNA repair protein through a novel activation motif. 1827 Jun 79

Most disease resistance genes in plants encode NBS-LRR proteins. However, in woody species, little is known about the evolutionary history of these genes. Here, we identified 459 and 330 respective NBS-LRRs in grapevine and poplar genomes. We subsequently investigated protein motif composition, phylogenetic relationships and physical locations. We found significant excesses of recent duplications in perennial species, compared with those of annuals, represented by rice and Arabidopsis. Consequently, we observed higher nucleotide identity among paralogs and a higher percentage of NBS-encoding genes positioned in numerous clusters in the grapevine and poplar. These results suggested that recent tandem duplication played a major role in NBS-encoding gene expansion in perennial species. These duplication events, together with a higher probability of recombination revealed in this study, could compensate for the longer generation time in woody perennial species e.g. duplication and recombination could serve to generate novel resistance specificities. In addition, we observed extensive species-specific expansion in TIR-NBS-encoding genes. Non-TIR-NBS-encoding genes were poly- or paraphyletic, i.e. genes from three or more plant species were nested in different clades, suggesting different evolutionary patterns between these two gene types.
Mol Genet Genomics 2008 Sep
PMID:Recent duplications dominate NBS-encoding gene expansion in two woody species. 1856 45

The Nijmegen breakage syndrome protein Nbs1 is a component of the MRN (Mre11-Rad50-Nbs1) complex, central to the DNA damage response. While Nbs1 is generally believed to encompass a forkhead-associated domain linked to a breast cancer C-terminal (BRCT) domain, to date there is no experimental information on its three-dimensional structure. Through nuclear magnetic resonance (NMR) three-dimensional structure determination, we demonstrate that there is a second BRCT domain (BRCT2) in Nbs1. The domain has the characteristic BRCT topology, but with a long insertion shown to be flexible by NMR relaxation measurements. In the absence of sequence similarity to other proteins, a search for structural analogs of BRCT2 returned the second BRCT domain of the tandem BRCT repeats of cell cycle checkpoint proteins MDC1 (mediator of DNA damage checkpoint protein 1) and BRCA1 (breast cancer protein 1), suggesting that like MDC1 and BRCA1, Nbs1 also possesses tandem BRCT domains with phosphoprotein binding ability. Structure-based single point mutations in human Nbs1 were evaluated in vivo and revealed that BRCT2 is essential for an MDC1-dependent relocalization of Nbs1 to DNA damage sites, most likely through a direct interaction of Nbs1 tandem BRCT domains with phosphorylated MDC1.
J Mol Biol 2008 Aug 29
PMID:Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites. 1858 74

Ataxia telangiectasia and Rad3-related (ATR) is a phosphoinositol-3-kinase like kinase (PIKK) that initiates a signal transduction response to replication fork stalling. Defects in ATR signalling have been reported in several disorders characterized by microcephaly and growth delay. Here, we gain insight into factors influencing the ATR signalling pathway and consider how they can be exploited for diagnostic purposes. Activation of ATR at stalled replication forks leads to intra-S and G2/M phase checkpoint arrest. ATR also phosphorylates gamma-H2AX at single-stranded (ss) DNA regions generated during nucleotide excision repair (NER) in non-replicating cells, but the critical analysis of any functional consequence has not been reported. Here, we show that UV irradiation of G2 phase cells causes ATR-dependent but replication-independent G2/M checkpoint arrest. This process requires the Nbs1 N-terminus encompassing the FHA and BRCT domains but not the Nbs1 C-terminus in contrast to ATM-dependent activation of G2/M arrest in response to ionizing radiation. Thus, Nbs1 has a function in ATR signalling in a manner distinct to any role at stalled replication forks. Replication-independent ATR signalling also requires the mediator proteins, 53BP1 and MDC1, providing direct evidence for their role in ATR signalling, but not H2AX. Finally, the process is activated in Cockayne's syndrome but not Xeroderma pigmentosum group A cells providing evidence that ssDNA regions generated during NER are the ATR-pathway-specific activating lesion. Replication-independent G2/M checkpoint arrest represents a suitable assay to specifically identify patients with defective ATR signalling, including Seckel syndrome, Nijmegen breakage syndrome and MCPH-1-dependent primary microcephaly.
Hum Mol Genet 2008 Oct 15
PMID:Replication independent ATR signalling leads to G2/M arrest requiring Nbs1, 53BP1 and MDC1. 1866 57

We examined patterns of nucleotide diversity at a genomic region containing two linked candidate disease resistance (NBS-LRR) genes in seven populations of the outcrossing plant Arabidopsis lyrata. In comparison with two adjacent control genes and neutral reference genes across the genome, the NBS-LRR genes exhibited elevated nonsynonymous variation and a large number of major-effect polymorphisms causing early stop codons and/or frameshift mutations. In contrast, analysis of synonymous diversity provided no evidence that the region was subject to long-term balancing selection or recent selective sweeps in any of the seven populations surveyed. Also in contrast with earlier surveys of one of these R genes, there was no evidence that the resistance genes or the major-effect mutations were subject to elevated differentiation between populations. We suggest that conditional neutrality in the absence of the corresponding pathogen, rather than long-term balancing selection or local adaptation, may in some circumstances be a significant cause of elevated functional polymorphism at R genes. In contrast with the R genes, analysis of diversity and differentiation at the flanking FERONIA locus showed high population divergence, suggesting local adaptation on this locus controlling male-female signalling during fertilization.
Mol Ecol 2008 Dec
PMID:Conditional neutrality at two adjacent NBS-LRR disease resistance loci in natural populations of Arabidopsis lyrata. 1899 6

Nijmegen breakage syndrome arises from hypomorphic mutations in the NBN gene encoding nibrin, a component of the MRE11/RAD50/nibrin (MRN) complex. In mammalian cells, the MRN complex localizes to the nucleus, where it plays multiple roles in the cellular response to DNA double-strand breaks. In the current study, sequences in mouse nibrin required to direct the nuclear localization of the MRN complex were identified by site-specific mutagenesis. Unexpectedly, nibrin was found to contain both nuclear localizing signal (NLS) sequences and a nuclear export signal (NES) sequence whose functions were confirmed by mutagenesis. Both nuclear import and export sequences were active in vivo. Disruption of either the NLS or NES sequences of nibrin significantly altered the cellular distribution of nibrin and Mre11 and impaired survival after exposure to ionizing radiation. Mutation of the NES sequence in nibrin slowed the turnover of phosphorylated nibrin after irradiation, indicating that nuclear export of nibrin may function, in part, to downregulate posttranslationally modified MRN complex components after DNA damage responses are complete.
Mol Cell Biol 2009 Feb
PMID:Nuclear export of NBN is required for normal cellular responses to radiation. 1907 3

Based on the conserved regions of known resistance genes, a NBS-LRR type CCN resistance gene analog was isolated from the CCN resistant E-10 near isogenic lines (NILs) of wheat, designated as CreZ (GenBank Acc. N: EU327996). It contained a complete ORF that was 2775 bp in length and encoded 924 amino acids. Sequence comparison indicated that it shared 92% nucleotide and 87% amino acid identity with those of the known CCN-resistance gene Cre3 and had similar characteristic conserved motifs as those in other established NBS-LRR disease resistance genes. The expression profiling of CreZ indicated that it was specifically expressed in the roots of resistant plants and real-time PCR analysis demonstrated that expression levels drastically increased when the plants were inoculated with cereal cyst nematodes. It could be inferred, then, that CreZ belongs to the NBS-LRR resistance gene family and is a candidate gene for potential resistance to the cereal cyst nematode.
Mol Biol (Mosk)
PMID:[Characterization and expression profiling of a novel cereal cyst nematode resistance gene analog in wheat]. 1914 Mar 29

Many microorganisms interact with plants but information is insufficient concerning requirements for plant colonization and if interactions become beneficial or detrimental. Pretreatment of oilseed rape (Brassica napus) with Bacillus results in disease suppression upon challenge with pathogens. We have studied transcriptome effects on oilseed rape primed with the Bacillus amyloliquefaciens 5113 biocontrol strain and compared that with effects of the fungal pathogen Botrytis cinerea. Using the cDNA-AFLP technique 21,700 transcript fragments were obtained of which 120 were differentially expressed and verified by northern blot analysis for selected transcripts. Priming with Bacillus caused greater effect on leaf than root transcripts where sequencing and BLAST analysis suggested many of the transcripts to be involved in metabolism and bioenergy. Bacillus and Botrytis treatment also changed metabolic gene expression in addition to signaling and transcription control genes as well as a potential disease resistance (TIR-NBS-LRR) gene. The pathogen provoked non-primed plant profile was less dominated by metabolism than Bacillus and Bacillus-Botrytis treated plants. Several transcripts were homologues to unknown genes in the different treatments. Altogether Bacillus treatment of roots cause a systemic gene expression in leaves suggested to result in a metabolic reprogramming as a major event during priming.
Plant Mol Biol 2009 May
PMID:Transcript profiling of oilseed rape (Brassica napus) primed for biocontrol differentiate genes involved in microbial interactions with beneficial Bacillus amyloliquefaciens from pathogenic Botrytis cinerea. 1918 61

Probenazole (3-allyloxy-1,2-benzothiazole 1,1-dioxide, PBZ) is a bactericide and fungicide that acts by inducing plant defense systems. It has been shown to induce the expression of NBS-LRR genes like RPR1 (rice probenazole-response gene) in rice (Oryza sativa L.) and systemic acquired resistance (SAR)-like disease resistance. Two maize (Zea mays L.) genes Zmnbslrr1 (a NBS-LRR gene, cloned from a disease resistance analog PIC11 based) and Zmgc1, (a putative guanylyl cyclase-like gene) have both been associated with quantitative resistance loci (QTL) for resistance to Fusarium graminearum. PIC11 was associated with Fusarium stalk rot and ZmGC1 showed resistance to Gibberella ear rot caused by F. graminearum. The objectives of the current study here were to characterize the Zmnbslrr1 gene and to determine whether it and Zmgc1 respond to the inducer PBZ. The transcript abundance of Zmnbslrr1 expression was significantly reduced in corn seedlings of the Gibberella ear rot resistant genotype CO387 48 h after PBZ treatment. In contrast, the transcript abundance of the maize Zmgc1 gene increased more than 10-fold 8h after the treatment. Therefore, the two genes do not appear to be coordinately regulated by PBZ.
Curr Issues Mol Biol 2009
PMID:Different responses of two genes associated with disease resistance loci in maize (Zea mays L.) to 3-allyloxy-1,2-benzothiazole 1,1-dioxide. 1919 68


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