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211.
The formation of a functional bipolar mitotic spindle is essential for genetic integrity. In human cells, the microtubule polymerase XMAP215/ch-Tog ensures spindle bipolarity by counteracting the activity of the microtubule-depolymerizing kinesin XKCM1/MCAK. Their antagonistic effects on microtubule polymerization confer dynamic instability on microtubules assembled in cell-free systems. It is, however, unclear if a similar interplay governs microtubule behavior in mammalian cells in vivo. Using real-time analysis of spindle assembly, we found that ch-Tog is required to produce or maintain long centrosomal microtubules after nuclear-envelope breakdown. In the absence of ch-Tog, microtubule assembly at centrosomes was impaired and microtubules were nondynamic. Interkinetochore distances and the lengths of kinetochore fibers were also reduced in these cells. Codepleting MCAK with ch-Tog improved kinetochore fiber length and interkinetochore separation but, surprisingly, did not rescue centrosomal microtubule assembly and microtubule dynamics. Our data therefore suggest that ch-Tog has at least two distinct roles in spindle formation. First, it protects kinetochore microtubules from depolymerization by MCAK. Second, ch-Tog plays an essential role in centrosomal microtubule assembly, a function independent of MCAK activity. Thus, the notion that the antagonistic activities of MCAK and ch-Tog determine overall microtubule stability is too simplistic to apply to human cells. 相似文献
212.
Receptor tyrosine kinases transmit and process extracellular cues by recruiting intracellular signaling proteins to sites of tyrosine phosphorylation. Using protein microarrays comprising virtually every human SH2 and PTB domain, we generated quantitative protein interaction maps for three well-studied receptors--EGFR, FGFR1 and IGF1R--using phosphopeptides derived from every intracellular tyrosine residue on each receptor, regardless of whether or not they are phosphorylated in vivo. We found that, in general, peptides derived from physiological sites of tyrosine phosphorylation bind to substantially more SH2 or PTB domains than do peptides derived from nonphysiological sites, supporting the idea that kinases and interaction domains co-evolve and suggesting that new sites arise predominantly through selection favoring advantageous interactions, rather than through selection disfavoring unwanted interactions. We also found substantial qualitative overlap in the recruitment profiles of these three receptors, suggesting that their different biological effects arise, at least in part, from quantitative differences in their affinities for the proteins they recruit. 相似文献
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214.
Zhang H Rider SD Henderson JT Fountain M Chuang K Kandachar V Simons A Edenberg HJ Romero-Severson J Muir WM Ogas J 《The Journal of biological chemistry》2008,283(33):22637-22648
CHD3 proteins are ATP-dependent chromatin remodelers that contribute to repression of developmentally regulated genes in both animal and plant systems. In animals, this repression has been linked to a multiple subunit complex, Mi-2/NuRD, whose constituents include a CHD3 protein, a histone deacetylase, and a methyl-CpG-binding domain protein. In Arabidopsis, PICKLE (PKL) codes for a CHD3 protein that acts during germination to repress expression of seed-associated genes. Repression of seed-associated traits is promoted in pkl seedlings by the plant growth regulator gibberellin (GA). We undertook a microarray analysis to determine how PKL and GA act to promote the transition from seed to seedling. We found that PKL and GA act in separate pathways to repress expression of seed-specific genes. Comparison of genomic datasets revealed that PKL-dependent genes are enriched for trimethylation of histone H3 lysine 27 (H3K27me3), a repressive epigenetic mark. Chromatin immunoprecipitation studies demonstrate that PKL promotes H3K27me3 in both germinating seedlings and in adult plants but do not identify a connection between PKL-dependent expression and acetylation levels. Taken together, our analyses illuminate a new pathway by which CHD3 remodelers contribute to repression in eukaryotes. 相似文献
215.
SLP-2 interacts with prohibitins in the mitochondrial inner membrane and contributes to their stability 总被引:1,自引:0,他引:1
Da Cruz S Parone PA Gonzalo P Bienvenut WV Tondera D Jourdain A Quadroni M Martinou JC 《Biochimica et biophysica acta》2008,1783(5):904-911
Stomatin is a member of a large family of proteins including prohibitins, HflK/C, flotillins, mechanoreceptors and plant defense proteins, that are thought to play a role in protein turnover. Using different proteomic approaches, we and others have identified SLP-2, a member of the stomatin gene family, as a component of the mitochondria. In this study, we show that SLP-2 is strongly associated with the mitochondrial inner membrane and that it interacts with prohibitins. Depleting HeLa cells of SLP-2 lead to increased proteolysis of prohibitins and of subunits of the respiratory chain complexes I and IV. Further supporting the role of SLP-2 in regulating the stability of specific mitochondrial proteins, we found that SLP-2 is up-regulated under conditions of mitochondrial stress leading to increased protein turnover. These data indicate that SLP-2 plays a role in regulating the stability of mitochondrial proteins including prohibitins and subunits of respiratory chain complexes. 相似文献
216.
Villanueva S Cespedes C Gonzalez AA Roessler E Vio CP 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,294(3):R819-R828
Recovery from acute renal failure (ARF) requires the replacement of injured cells by new cells that are able to restore tubule epithelial integrity. We have recently described the expression of nephrogenic proteins [Vimentin, neural cell adhesion molecule, basic fibroblast growth factor (bFGF), Pax-2, bone morphogen protein-7, Noggin, Smad 1-5-8, p-Smad, hypoxia-inducible factor-1alpha, vascular endothelial growth factor], in a time frame similar to that observed in kidney development, after ischemic ARF induced in an ischemia-reperfusion (I/R) model. Furthermore, we show that bFGF, a morphogen involved in mesenchyme/epithelial transition in kidney development, induces a reexpression of morphogenic proteins in an earlier time frame and accelerates the recovery process after renal damage. Herein, we confirm that renal morphogenes are modulated by bFGF and hypothesized that a decrease in bFGF receptor 2 (bFGFR2) levels by the use of antisense oligonucleotides diminishes the expression of morphogenes. Male Sprague-Dawley rats submitted to ischemic injury were injected with 112 microg/kg bFGFR2 antisense oligonucleotide (bFGFR2-ASO) followed by reperfusion. Rats were killed, and the expression of nephrogenic proteins and renal marker damage was analyzed by immunohistochemistry and immunoblot. Animals subjected to I/R treated with bFGFR2-ASO showed a significant reduction in morphogen levels (P < 0.05). In addition, we observed an increase in markers of renal damage: macrophages (ED-1) and interstitial alpha-smooth muscle actin. These results confirm that bFGF participates in the recovery process and that treatment with bFGFR2-ASO induces an altered expression of morphogen proteins. 相似文献
217.
218.
Picard M Csukly K Robillard ME Godin R Ascah A Bourcier-Lucas C Burelle Y 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,295(2):R659-R668
This study determined whether susceptibility to opening of the permeability transition pore (PTP) varies according to muscle phenotype represented by the slow oxidative soleus (Sol) and superficial white gastrocnemius (WG). Threshold for Ca2+-induced mitochondrial Ca2+ release following PTP opening was determined with a novel approach using permeabilized ghost myofibers. Threshold values for PTP opening were approximately threefold higher in fibers from WG compared with those from Sol (124+/-47 vs. 30.4+/-6.8 pmol Ca2+/mU citrate synthase). A similar phenomenon was also observed in isolated mitochondria (threshold: 121+/-60 vs. 40+/-10 nmol Ca2+/mg protein in WG and Sol), indicating that this was linked to differences in mitochondrial factors between the two muscles. The resistance of WG fibers to PTP opening was not related to the expression of putative protein modulators (cyclophilin D, adenylate nucleotide translocator-1, and voltage-dependent anion channels) or to difference in respiratory properties and occurred despite the fact that production of reactive oxygen species, which promote pore opening, was higher than in the Sol. However, endogenous matrix Ca2+ measured in mitochondria isolated under resting baseline conditions was approximately twofold lower in the WG than in the Sol (56+/-4 vs. 111+/-11 nmol/mg protein), which significantly accounted for the resistance of WG. Together, these results reveal fiber type differences in the sensitivity to Ca2+-induced PTP opening, which may constitute a physiological mechanism to adapt mitochondria to the differences in Ca2+ dynamics between fiber types. 相似文献
219.
220.
Jacques-Eric Gottenberg Jérémie Sellam Marc Ittah Frédéric Lavie Alexis Proust Habib Zouali Christelle Sordet Jean Sibilia Robert P Kimberly Xavier Mariette Corinne Miceli-Richard 《Arthritis research & therapy》2005,8(1):1-5
Polyclonal B cell activation might be related to pathogenic over-expression of B-cell-activating factor (BAFF) in primary Sjögren's syndrome (pSS) and other autoimmune diseases. We therefore investigated whether BAFF over-expression in pSS could be a primary, genetically determined event that leads to the disease. The complete BAFF gene was sequenced in Caucasian pSS patients and control individuals. The only single nucleotide polymorphism frequently observed, namely -871 T/C in the promoter region, was then genotyped in 162 French patients with pSS and 90 French control individuals. No significant differences in allele (T allele frequency: 49.7% in patients with pSS versus 50% in controls; P = 0.94) and genotype frequencies of BAFF polymorphism were detected between pSS patients and control individuals. BAFF gene polymorphism was not associated with a specific pattern of antibody secretion either. T allele carriers had significantly increased BAFF protein serum levels (mean values of 8.6 and 5.7 ng/ml in patients with TT and TC genotypes, respectively, versus 3.3 ng/ml in patients with CC genotype; P = 0.01), although no correlation was observed between BAFF polymorphism and mRNA level. In conclusion, BAFF gene polymorphism is neither involved in genetic predisposition to pSS nor associated with a specific pattern of antibody production. 相似文献