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Molecular Characterization of the SUMO-1 Modification of RanGAP1 and Its Role in Nuclear Envelope Association 总被引:13,自引:1,他引:12 下载免费PDF全文
The mammalian guanosine triphosphate (GTP)ase-activating protein RanGAP1 is the first example of a protein covalently linked to the ubiquitin-related protein SUMO-1. Here we used peptide mapping, mass spectroscopy analysis, and mutagenesis to identify the nature of the link between RanGAP1 and SUMO-1. SUMO-1 is linked to RanGAP1 via glycine 97, indicating that the last 4 amino acids of this 101– amino acid protein are proteolytically removed before its attachment to RanGAP1. Recombinant SUMO-1 lacking the last four amino acids is efficiently used for modification of RanGAP1 in vitro and of multiple unknown proteins in vivo. In contrast to most ubiquitinated proteins, only a single lysine residue (K526) in RanGAP1 can serve as the acceptor site for modification by SUMO-1. Modification of RanGAP1 with SUMO-1 leads to association of RanGAP1 with the nuclear envelope (NE), where it was previously shown to be required for nuclear protein import. Sufficient information for modification and targeting resides in a 25-kD domain of RanGAP1. RanGAP1–SUMO-1 remains stably associated with the NE during many cycles of in vitro import. This indicates that removal of RanGAP1 from the NE is not a required element of nuclear protein import and suggests that the reversible modification of RanGAP1 may have a regulatory role. 相似文献
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N. K. Arora Ekta Khare S. Singh D. K. Maheshwari 《World journal of microbiology & biotechnology》2010,26(5):811-816
Most of the legume crops are affected by metal stress present in the soil mainly due to contaminated agrochemicals and sewage
sludge. The effect of aluminium, and heavy metals copper, iron and molybdenum on growth and activity of enzymes of fast and
slow growing rhizobial sps. was studied. Sinorhizobium meliloti RMP5 was found to be more tolerant to metal stress than Bradyrhizobium BMP1. Both the strains were extremely sensitive to Al than other metals. Al was much more deleterious for the enzymatic activities
(nitrate reduction, nitrite reduction, nitrogenase and uptake hydrogenase) of strain RMP5 and BMP1. Cu showed inhibitory effect on growth and enzyme activities of Bradyrhizobium strain at all concentrations. However, in S. meliloti RMP5 all the tested enzymatic activities increased up to the concentration of 0.1 mM Cu. Fe enhanced the growth and enzyme activities
of S. meliloti RMP5 and Bradyrhizobium BMP1 up to 100 mM concentration. Mo enhanced all the tested enzymatic activities of S. meliloti RMP5 up to 1 mM. Nitrate and nitrite reduction activities of Bradyrhizobium BMP1 increased up to 1 mM concentration. However, nitrogenase and hydrogenase activities of Bradyrhizobium BMP1 got enhanced only up to 0.5 mM Mo. Both Fe and Mo are the key components of the enzyme nitrogenase and nitrate reductase
and enhanced the growth and enzyme activities of both the sps. The study of physiology of nitrogen fixing ability of both
fast and slow growing rhizobial strains reported that the supplementation of Mo and Fe in soils along with the biological
formulations will enhance the process of symbiotic nitrogen fixation. 相似文献
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Mohite PN Kuthe SA Thingnam SK Rohit MK Mahajan S Mahajan R 《Innovations (Philadelphia, Pa.)》2010,5(4):311-312
Because the use of percutaneous intervention is increasing for the closure of the patent ductus arteriosus, the procedure-related complications are also on rise, with migration of the device being most common. The routine practice is to remove the migrated duct occluder device under cardiopulmonary bypass. Amplatzer duct occluder used in a 4-month-old infant dislodged into the descending thoracic aorta. It was removed by the posterolateral thoracotomy under mild hypothermia through juxtaductal aortotomy between the aortic cross-clamps. The use of cardiopulmonary bypass is thus avoided. 相似文献
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Roy S Khanna V Mittra S Dhar A Singh S Mahajan DC Priyadarsiny P Davis JA Sattigeri J Saini KS Bansal VS 《Life sciences》2007,81(1):72-79
Thiazolidinediones (TZDs) are currently the most efficacious class of oral antidiabetics. However, they carry the burden of weight gain and haemodilution, which may lead to cardiovascular complications. The present study was designed to ascertain whether a combination of dipeptidyl peptidase IV (DPP IV) inhibitor with low dose of a thiazolidinedione absolves TZD associated weight gain and oedema without compromising its efficacy. In this study, we examined the efficacy and safety of lower dose (1 mg/kg/day) of rosiglitazone, a thiazolidinedione, in combination with 5 mg/kg/day dose of LAF-237 (vildagliptin), a known DPP IV inhibitor, in aged db/db mice after 14 days of treatment and compared the combination with therapeutic dose (10 mg/kg) of rosiglitazone. The combination therapy showed similar efficacy as that of 10 mg/kg/day rosiglitazone in lowering random blood glucose (53.8%, p<0.001 and 54.3%, p<0.001 respectively), AUC ((0-120) min) during oral glucose tolerance test (OGTT) (38.6 %, p<0.01; 38.3%, p<0.01 respectively) and triglyceride levels (63.9% and 61% respectively; p<0.01). Plasma active glucagon like peptide-1 (GLP-1) and insulin levels were found to be elevated significantly (p<0.01 and p<0.05 respectively) in both LAF-237 and combination treated groups following oral glucose load. LAF-237 alone had no effect on random glucose and glucose excursion during OGTT in severely diabetic db/db mice. Interestingly, the combination treatment showed no significant increase in body weight as compared to the robust weight gain by therapeutic dose of rosiglitazone. Rosiglitazone at 10 mg/kg/day showed significant reduction (p<0.05) in haematocrit, RBC count, haemoglobin pointing towards haemodilution associated with increased mRNA expression of Na(+), K(+)-ATPase-alpha and epithelial sodium channel gamma (ENaCgamma) in kidney. The combination therapy escaped these adverse effects. The results suggest that combination of DPP IV inhibitor with low dose of thiazolidinedione can interact synergistically to represent a therapeutic advantage for the clinical treatment of type 2 diabetes without the adverse effects of haemodilution and weight gain associated with thiazolidinediones. 相似文献
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The role of mitochondria in causing diseases is becoming evident as more and more studies are focusing on this organelle of
the cell. This is largely attributed to its reactive oxygen species (ROS) production property. In the context of diabetes,
ROS is suggested to trigger different forms of insulin resistance involving different mechanisms. The suggestive role of a
mtDNA variant G10398A in increasing ROS production and the impaired response to oxidative stress due to T16189C variant is
worth addressing as genetic susceptibility factors in type 2 diabetes mellitus (T2DM). A case control study on 312 T2DM cases
and ethnically matched 466 controls involving two North Indian populations, referred as cohort 1 and cohort 2 (in a replicative
study), was undertaken to test such a genetic association. A statistically significant association was observed for 10398A
allele in both the cohorts [cohort1 (OR = 2.67 95% CI 1.77–4.00); cohort2 (OR = 1.76 95%CI 1.12–2.77)]. The analysis of G10398A/T16189C
haplotypic combinations revealed that 10398A/16189C haplotype provides a risk in both the cohorts. To sum up the study suggests
that 10398A and 16189C alleles provide susceptiblity to T2DM independently as well as together. 相似文献
40.
Dziva F Mahajan A Cameron P Currie C McKendrick IJ Wallis TS Smith DG Stevens MP 《FEMS microbiology letters》2007,271(2):258-264
Enterohaemorrhagic Escherichia coli (EHEC) comprise a group of zoonotic diarrhoeal pathogens of worldwide importance. Cattle are a key reservoir; however the molecular mechanisms that promote persistent colonization of the bovine intestines by EHEC are ill-defined. The large plasmid of EHEC O157:H7 encodes several putative virulence factors. Here, it is reported that the pO157-encoded Type V-secreted serine protease EspP influences the intestinal colonization of calves. To dissect the basis of attenuation, a bovine primary rectal epithelial cell line was developed. Adherence of E. coli O157:H7 to such cells was significantly impaired by espP mutation but restored upon addition of highly purified exogenous EspP. Data of this study add to the growing body of evidence that cytotoxins facilitate intestinal colonization by EHEC. 相似文献