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271.
Molecular requirements for kinetochore-associated microtubule formation in mammalian cells 总被引:1,自引:0,他引:1
In centrosome-containing cells, microtubules nucleated at centrosomes are thought to play a major role in spindle assembly. In addition, microtubule formation at kinetochores has also been observed, most recently under physiological conditions in live cells. The relative contributions of microtubule formation at kinetochores and centrosomes to spindle assembly, and their molecular requirements, remain incompletely understood. Using mammalian cells released from nocodazole-induced disassembly, we observed microtubule formation at centrosomes and at Bub1-positive sites on chromosomes. Kinetochore-associated microtubules rapidly coalesced into pole-like structures in a dynein-dependent manner. Microinjection of excess importin-beta or depletion of the Ran-dependent spindle assembly factor, TPX2, blocked kinetochore-associated microtubule formation, enhanced centrosome-associated microtubule formation, but did not prevent chromosome capture by centrosomal microtubules. Depletion of the chromosome passenger protein, survivin, reduced microtubule formation at kinetochores in an MCAK-dependent manner. Microtubule formation in cells depleted of Bub1 or Nuf2 was indistinguishable from that in controls. Our data demonstrate that microtubule assembly at centrosomes and kinetochores is kinetically distinct and differentially regulated. The presence of microtubules at kinetochores provides a mechanism to reconcile the time required for spindle assembly in vivo with that observed in computer simulations of search and capture. 相似文献
272.
In all organisms, haem is post-translationally and covalently attached to c apocytochromes to produce c holocytochromes via a process called c-type cytochromes maturation, which involves numerous components. In bacteria it was not clear which of these components catalyses the extracytoplasmic haem-apocytochrome ligation per se. In this issue of Molecular Microbiology, Feissner and colleagues report that a single polypeptide from Helicobacter pylori, corresponding to the fusion of two proteins found in other organisms, performs haem ligation to a coexpressed Bordetella pertussis apocytochrome c in an Escherichia coli mutant lacking its own cytochrome c maturation proteins. This simple experimental system pinpoints the components catalysing extracytoplasmic covalent haem ligation and raises intriguing issues about the requirements for delivery of haem and apocytochrome c substrates to produce c holocytochromes. 相似文献
273.
Upstream stimulatory factor-2 regulates steroidogenic factor-1 expression in endometriosis 总被引:1,自引:0,他引:1
274.
Durdagi S Mavromoustakos T Papadopoulos MG 《Bioorganic & medicinal chemistry letters》2008,18(23):6283-6289
For the first time, a set of experimentally reported [60] fullerene derivatives were subjected to the 3D-QSAR/CoMFA and CoMSIA studies. The aim of this study is to propose a series of novel [60] fullerene-based inhibitors with optimal binding affinity for the HIV-1 PR enzyme. The position of the template molecule at the cavity of HIV-1 PR was optimized and 3D QSAR models were developed. Relative contributions of steric/electrostatic fields of the 3D-QSAR/CoMFA and CoMSIA models have shown that steric effects govern the bioactivity of the compounds, but electrostatic interactions play also an important role.The de novo drug design Leapfrog simulations provided a series of novel compounds with predicted improved inhibition effect. 相似文献
275.
Dilek Din?ol Ali Arican Arzu Ensari Serdar Akyar Yaar Bedük Abdülkadir Cengiz 《Cancer immunology, immunotherapy : CII》1999,16(2):134-138
A 53-year-old man with triple renal neoplasms in his left kidney presented. He was initially diagnosed intermediate grade
non-Hodgkin’s lymphoma (NHL) which involved gastro-intestinal tract, left kidney, liver and pancreas. He underwent left nefrectomy
because of a persistent renal mass after the completion of chemotherapy. The large renal mass revealed a renal cell carcinoma
(RCC). Additionally, multiple small nodules of non-Hodgkin’s lymphoma and a solitary leiomyoma were observed. 相似文献
276.
277.
278.
Aromatase in endometriosis and uterine leiomyomata 总被引:7,自引:0,他引:7
Bulun SE Imir G Utsunomiya H Thung S Gurates B Tamura M Lin Z 《The Journal of steroid biochemistry and molecular biology》2005,95(1-5):57-62
Endometrial tissue from uterine disease-free women does not exhibit aromatase activity. In contrast, aromatase enzyme activity and mRNA levels are readily detectable in endometriosis. PGE2 stimulates both aromatase expression and activity in endometriotic stromal cells via promoter II region of the aromatase gene. This results in local production of estradiol, which induces PGE2 formation and establishes a positive feedback cycle. This mechanism seems to contribute to continuous production of estradiol and PGE2. Aromatase mRNA levels and enzyme activity are also present in uterine leiomyomata that are estrogen-dependent benign tumors of the myometrium. Successful treatment of endometriosis and uterine leiomyomata using aromatase inhibitors by recent pilot trials underscores the clinical significance of these molecular studies. 相似文献
279.
Tamura M Sebastian S Yang S Gurates B Ferrer K Sasano H Okamura K Bulun SE 《The Journal of biological chemistry》2002,277(29):26208-26216
280.
Ion channels: recent progress and prospects 总被引:3,自引:0,他引:3
Determination of the crystal structure of the KcsA potassium channel and its subsequent refinement at 2 A resolution have stimulated much interest in modelling of ion channels. Here we review the recent developments in ion channels research, focusing especially on the question of structure-function relationships, and discuss how permeation models based on Brownian and molecular dynamics simulations can be used fruitfully in this endeavour. 相似文献