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71.
Bin He Xiaomeng Yu Moran Margolis Xianghua Liu Xiaohong Leng Yael Etzion Fei Zheng Nan Lu Florante A. Quiocho Dganit Danino Zheng Zhou 《Molecular biology of the cell》2010,21(4):610-629
Dynamins are large GTPases that oligomerize along membranes. Dynamin''s membrane fission activity is believed to underlie many of its physiological functions in membrane trafficking. Previously, we reported that DYN-1 (Caenorhabditis elegans dynamin) drove the engulfment and degradation of apoptotic cells through promoting the recruitment and fusion of intracellular vesicles to phagocytic cups and phagosomes, an activity distinct from dynamin''s well-known membrane fission activity. Here, we have detected the oligomerization of DYN-1 in living C. elegans embryos and identified DYN-1 mutations that abolish DYN-1''s oligomerization or GTPase activities. Specifically, abolishing self-assembly destroys DYN-1''s association with the surfaces of extending pseudopods and maturing phagosomes, whereas inactivating guanosine triphosphate (GTP) binding blocks the dissociation of DYN-1 from these membranes. Abolishing the self-assembly or GTPase activities of DYN-1 leads to common as well as differential phagosomal maturation defects. Whereas both types of mutations cause delays in the transient enrichment of the RAB-5 GTPase to phagosomal surfaces, only the self-assembly mutation but not GTP binding mutation causes failure in recruiting the RAB-7 GTPase to phagosomal surfaces. We propose that during cell corpse removal, dynamin''s self-assembly and GTP hydrolysis activities establish a precise dynamic control of DYN-1''s transient association to its target membranes and that this control mechanism underlies the dynamic recruitment of downstream effectors to target membranes. 相似文献
72.
Emily Lipsitz Ganesh Moorthy Yael Mosse Elizabeth Fox Peter C. Adamson 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(25):2369-2373
We describe a selective and a highly sensitive high-performance liquid chromatography–electron spray ionization-collision induced dissociation-tandem mass spectrometry (HPLC–ESI-CID-MS/MS) assay for the Aurora A kinase inhibitor MLN8237 in human plasma. The intra-day precision based on the standard deviation of replicates of quality control samples ranged from 0.2 to 4% and with accuracy ranging from 96 to 102%. The inter-day precision ranged from 0.5 to 7% and the accuracy ranged from 93 to 105%. Stability studies showed that MLN8237 was stable both during the expected conditions for sample preparation and storage. The lower limit of quantification for MLN8237 was 5 ng/mL. The analytical method showed excellent sensitivity, precision, and accuracy. This method is robust and is being successfully employed in a Children's Oncology Group Phase 1 Consortium study of MLN8237 in children with cancer. 相似文献
73.
74.
Living with p53, dying of p53 总被引:6,自引:0,他引:6
The p53 tumor suppressor protein acts as a major defense against cancer. Among its most distinctive features is the ability to elicit both apoptotic death and cell cycle arrest. In this issue of Cell, Das et al. (2007) and Tanaka et al. (2007) provide new insights into the mechanisms that dictate the life and death decisions of p53. 相似文献
75.
76.
Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, encoding type II transmembrane serine protease matriptase
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Basel-Vanagaite L Attia R Ishida-Yamamoto A Rainshtein L Ben Amitai D Lurie R Pasmanik-Chor M Indelman M Zvulunov A Saban S Magal N Sprecher E Shohat M 《American journal of human genetics》2007,80(3):467-477
In this article, we describe a novel autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair. Using homozygosity mapping, we mapped the disease locus to 11q24.3-q25. We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(-/-)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs. Mutation analysis revealed a missense mutation, G827R, in the highly conserved peptidase S1-S6 domain. Marked skin hyperkeratosis due to impaired degradation of the stratum corneum corneodesmosomes was observed in the affected individuals, which suggests that matriptase plays a significant role in epidermal desquamation. 相似文献
77.
Burgermeister E Chuderland D Hanoch T Meyer M Liscovitch M Seger R 《Molecular and cellular biology》2007,27(3):803-817
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascade plays a central role in intracellular signaling by many extracellular stimuli. One target of the ERK cascade is peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that promotes differentiation and apoptosis. It was previously demonstrated that PPARgamma activity is attenuated upon mitogenic stimulation due to phosphorylation of its Ser84 by ERKs. Here we show that stimulation by tetradecanoyl phorbol acetate (TPA) attenuates PPARgamma's activity in a MEK-dependent manner, even when Ser84 is mutated to Ala. To elucidate the mechanism of attenuation, we found that PPARgamma directly interacts with MEKs, which are the activators of ERKs, but not with ERKs themselves, both in vivo and in vitro. This interaction is facilitated by MEKs' phosphorylation and is mediated by the basic D domain of MEK1 and the AF2 domain of PPARgamma. Immunofluorescence microscopy and subcellular fractionation revealed that MEK1 exports PPARgamma from the nucleus, and this finding was supported by small interfering RNA knockdown of MEK1 and use of a cell-permeable interaction-blocking peptide, which prevented TPA-induced export of PPARgamma from the nucleus. Thus, we show here a novel mode of downregulation of PPARgamma by its MEK-dependent redistribution from the nucleus to the cytosol. This unanticipated role for the stimulation-induced nuclear shuttling of MEKs shows that MEKs can regulate additional signaling components besides the ERK cascade. 相似文献
78.
The N terminus of the Aeromonas salmonicida ADP-ribosylating toxin AexT displays in vitro GTPase-activating protein (GAP) activity for Rac1, CDC42, and RhoA. HeLa cells transfected with the AexT N terminus exhibit rounding and actin disordering. We propose that the Aeromonas salmonicida AexT toxin is a novel member of the growing family of bacterial RhoGAPs. 相似文献
79.
Vinokur V Leibowitz G Grinberg L Eliashar R Berenshtein E Chevion M 《Redox report : communications in free radical research》2007,12(6):246-256
Both type 1 and type 2 diabetes (insulin-dependent and non-insulin dependent diabetes, respectively) are associated with increased risk for microvascular and macrovascular complications including retinopathy, neuropathy, nephropathy and atherosclerosis. Type 2 diabetes markedly increases the risk for cardiovascular morbidity and mortality, which has major public health implications. In this review, molecular mechanisms pertaining to diabetes-induced heart pathology are addressed. 相似文献
80.
María Sol Gaspe Yael Mariana Provecho Romina Valeria Piccinali Ricardo Esteban Gürtler/ 《Memórias do Instituto Oswaldo Cruz》2015,110(3):310-318
House re-invasion by native triatomines after insecticide-based control campaigns
represents a major threat for Chagas disease vector control. We conducted a
longitudinal intervention study in a rural section (Area III, 407 houses) of Pampa
del Indio, northeastern Argentina, and used wing geometric morphometry to compare
pre-spray and post-spray (re-infestant bugs) Triatoma infestans
populations. The community-wide spraying with pyrethroids reduced the prevalence of
house infestation by T. infestans from 31.9% to < 1% during a
four-year follow-up, unlike our previous studies in the neighbouring Area I. Two
groups of bug collection sites differing in wing shape variables before interventions
(including 221 adults from 11 domiciles) were used as a reference for assigning 44
post-spray adults. Wing shape variables from post-spray, high-density bug colonies
and pre-spray groups were significantly different, suggesting that re-infestant
insects had an external origin. Insects from one house differed strongly in wing
shape variables from all other specimens. A further comparison between insects from
both areas supported the existence of independent re-infestation processes within the
same district. These results point to local heterogeneities in house re-infestation
dynamics and emphasise the need to expand the geographic coverage of vector
surveillance and control operations to the affected region. 相似文献