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Mutant

About: Mutant is a research topic. Over the lifetime, 74520 publications have been published within this topic receiving 3477079 citations.


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Journal ArticleDOI
TL;DR: Administration of 17-AAG markedly ameliorated motor impairments in the SBMA transgenic mouse model without detectable toxicity and would provide a new therapeutic approach to SBMA and probably to other related neurodegenerative diseases.
Abstract: Heat-shock protein 90 (Hsp90) functions as part of a multichaperone complex that folds, activates and assembles its client proteins. Androgen receptor (AR), a pathogenic gene product in spinal and bulbar muscular atrophy (SBMA), is one of the Hsp90 client proteins. We examined the therapeutic effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent Hsp90 inhibitor, and its ability to degrade polyglutamine-expanded mutant AR. Administration of 17-AAG markedly ameliorated motor impairments in the SBMA transgenic mouse model without detectable toxicity, by reducing amounts of monomeric and aggregated mutant AR. The mutant AR showed a higher affinity for Hsp90-p23 and preferentially formed an Hsp90 chaperone complex as compared to wild-type AR; mutant AR was preferentially degraded in the presence of 17-AAG in both cells and transgenic mice as compared to wild-type AR. 17-AAG also mildly induced Hsp70 and Hsp40. 17-AAG would thus provide a new therapeutic approach to SBMA and probably to other related neurodegenerative diseases.

377 citations

Journal ArticleDOI
TL;DR: AMS plays a crucial role in tapetal cell development and the post-meiotic transcriptional regulation of microspore development within the developing anther in Arabidopsis thaliana.
Abstract: Visual screening of a T-DNA mutagenised population of Arabidopsis thaliana for an absence of silique elongation lead to the isolation of the aborted microspores (ams) mutant that shows a sporophytic recessive male sterile phenotype. Homozygous mutant plants are completely devoid of mature pollen. Pollen degeneration occurs shortly after release of the microspores from the tetrad, prior to pollen mitosis I. Premature tapetum and microspore degeneration are the primary defects caused by this lesion, while a secondary effect is visualised in the stamen filaments, which are reduced in length and lie beneath the receptive stigma at flower opening. The disrupted gene was isolated and revealed a T-DNA element to be inserted into the eighth exon of a basic helix-loop-helix (bHLH) gene located on chromosome II. This protein sequence contains a basic DNA binding domain and two alpha helices separated by a loop, typical of a transcription factor belonging to the MYC sub family of bHLH genes. Therefore, AMS plays a crucial role in tapetal cell development and the post-meiotic transcriptional regulation of microspore development within the developing anther.

377 citations

Journal ArticleDOI
06 Sep 1996-Cell
TL;DR: Results are shown here demonstrating that the expression of par-4 in NIH-3T3 cells induces morphological changes typical of apoptosis, which are abrogated by cotransfection of either wild-type zeta PKC or lambda/LPKC, but not by their respective kinase-inactive mutants.

377 citations

Journal ArticleDOI
TL;DR: Mutants of Escherichia coli K-12 requiring considerably elevated concentrations of potassium for growth are readily obtained as double mutants combining a kdp mutation with a mutation in one or more of five other loci, referred to as trk, for transport of K, because these mutations result in alterations in K transport.
Abstract: Mutants of Escherichia coli K-12 requiring considerably elevated concentrations of potassium for growth are readily obtained as double mutants combining a kdp mutation with a mutation in one or more of five other loci. These loci are referred to as trk, for transport of K, because these mutations result in alterations in K transport. The kdp mutation is essential in the isolation and identification of this type of mutant; in a Kdp(+) strain, the presence of a trk mutation does not prevent growth of the strain in media containing very low concentrations of K. The trk loci are widely scattered over the E. coli chromosome; none of them is very near any other trk locus or near the kdp genes.

377 citations

Journal ArticleDOI
TL;DR: A model is presented that postulates that hipA7 increases the basal level of (p)ppGpp synthesis, allowing a significantly greater percentage of cells in a population to assume a persistent, antibiotic‐insensitive state by potentiating a rapid transition to a dormant state upon application of stress.
Abstract: Summary The ability of a high frequency (10−2) of Escherichia coli to survive prolonged exposure to penicillin antibiotics, called high persistence, is associated with mutations in the hipA gene. The hip operon is located in the chromosomal terminus near dif and consists of two genes, hipA and hipB. The wild-type hipA gene encodes a toxin, whereas hipB encodes a DNA-binding protein that autoregulates expression of the hip operon and binds to HipA to nullify its toxic effects. We have characterized the hipA7 allele, which confers high persistence, and established that HipA7 is non-toxic, contains two mutations (G22S and D291A) and that both mutations are required for the full range of phenotypes associated with hip mutants. Furthermore, expression of hipA7 in the absence of hipB is sufficient to establish the high persistent phenotype, indicating that hipB is not required. There is a strong correlation between the frequency of persister cells generated by hipA7 strains and cell density, with hipA7 strains generating a 20-fold higher frequency of persisters as cultures approach stationary phase. It is also demonstrated that relA knock-outs diminish the high persistent phenotype in hipA7 mutants and that relA spoT knock-outs eliminate high persistence altogether, suggesting that hipA7 facilitates the establishment of the persister state by inducing (p)ppGpp synthesis. Consistent with this proposal, ectopic expression of relA′ from a plasmid was shown to increase the number of persistent cells produced by hipA7 relA double mutants by 100-fold or more. A model is presented that postulates that hipA7 increases the basal level of (p)ppGpp synthesis, allowing a significantly greater percentage of cells in a population to assume a persistent, antibiotic-insensitive state by potentiating a rapid transition to a dormant state upon application of stress.

376 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
20237,150
20226,747
20211,630
20201,916
20191,849