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Suzanne Camus Sergio Menéndez Kenneth Fernandes Nelly Kua Geng Liu Dimitris P. Xirodimas David P. Lane Jean-Christophe Bourdon 《Cell cycle (Georgetown, Tex.)》2012,11(8):1646-1655
The discovery that the single p53 gene encodes several different p53 protein isoforms has initiated a flurry of research into the function and regulation of these novel p53 proteins. Full-length p53 protein level is primarily regulated by the E3-ligase Mdm2, which promotes p53 ubiquitination and degradation. Here, we report that all of the novel p53 isoforms are ubiquitinated and degraded to varying degrees in an Mdm2-dependent and -independent manner, and that high-risk human papillomavirus can degrade some but not all of the novel isoforms, demonstrating that full-length p53 and the p53 isoforms are differentially regulated. In addition, we provide the first evidence that Mdm2 promotes the NEDDylation of p53β. Altogether, our data indicates that Mdm2 can distinguish between the p53 isoforms and modify them differently. 相似文献
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Random Amplified Polymorphic DNA Variation among and within Selected Ixora (Rubiaceae) Populations and Mutants 总被引:1,自引:0,他引:1
RAJASEGER G.; TAN H. T. W.; TURNER I. M.; SAW L. G.; KUMAR P. P. 《Annals of botany》1999,84(2):253-257
Random amplified polymorphic DNA (RAPD) analysis was used tostudy variation among and within selectedIxora (Rubiaceae) populationsand mutants. Six populations of I. congesta yielded identicalbanding patterns suggesting genetic uniformity of this species.However, six populations of I. coccinea varieties (three red-flowered,two yellow-flowered and one red-flowered wild-type) exhibitedinfraspecific differences in RAPD profiles. Small and largeleaves of an atavistic mutant cultivar of I. coccinea were alsosubjected to RAPD analysis. An extra band was amplified in thelarge leaves that was absent in small leaves, suggesting thatthe phenotypic alteration in this taxon is due to genetic mutationrather than epigenetic changes. Similarly, an extra band wasdetected in the white sectors of I. Variegated compared to thegreen sectors, suggesting that the shoot apical meristems ofthis cultivar exist as a genetic chimera. DNA gel blot hybridizationwas performed to confirm the specificities of selected bands.Our study indicates that differences among individuals of variouspopulations and mutants may be detected using RAPD markers.Copyright 1999 Annals of Botany Company Ixora L., variegated variety, RAPD fingerprinting, DNA gel blot, intraspecific genetic similarity, atavistic mutant. 相似文献
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Genetic analysis of sterile mutants in the dpy-5 unc-13 (I) genomic region of Caenorhabditis elegans
Essential genes were identified in the 1.5-map unit dpy-5 unc-13 region of chromosome I in the Caenorhabditis elegans genome by rescuing lethal mutations using the duplication sDp2. In this paper, we report the mapping and complementation testing of lethal mutations, 45 of which identify 18 new, essential
genes. This analysis brings the number of essential genes defined by the sDp2 rescue of lethal mutants to 97; 64 of these map between dpy-5 and unc-13. 61% of these essential genes are identified by more than one allele. Positioning of the mutations was done using the breakpoints
of six duplications. The mutant phenotypes of 14 loci essential for fertility were characterized by Nomarski microscopy and
DAPI staining. None of the mutants were rescued by wild-type male sperm. The cytological data showed that four genes produced
mutants with defects in gonadogenesis, let-395, let-603, let-605 and let-610. Mutations in seven genes, let-355, let-367, let-384, let-513, let-544, let-545 and let-606, affected germ cell proliferation or gametogenesis. Mutants for the remaining three genes, let-370, let-599 and let-604, produced eggs that failed to develop or hatch, thereby acting as maternal effect lethals. We observed a nonrandom distribution
of arrest phenotypes with regard to map position.
Received: 8 May 1996 / Accepted : 27 January 1997 相似文献
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Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction
osteogenesis. These studies have demonstrated that intermittent PTH1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal
stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced
bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH1-34 treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing
in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the
appropriate patient population for PTH1-34 therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications)
and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering. 相似文献