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1.
Tokunaga F Nakagawa T Nakahara M Saeki Y Taniguchi M Sakata S Tanaka K Nakano H Iwai K 《Nature》2011,471(7340):633-636
Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM, symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-κB essential modulator; also known as IKBKG). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density) gene are responsible for the cpdm phenotype in mice. SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-κB activation through conjugation of linear polyubiquitin chains to NEMO. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-κB. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP (also known as RNF31). Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-α- and CD40-mediated activation of NF-κB in mouse embryonic fibroblasts (MEFs) or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-κB activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-κB activation in various disorders. 相似文献
2.
Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor 总被引:39,自引:0,他引:39
Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor. 相似文献
3.
Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40 总被引:32,自引:0,他引:32
Itoh Y Kawamata Y Harada M Kobayashi M Fujii R Fukusumi S Ogi K Hosoya M Tanaka Y Uejima H Tanaka H Maruyama M Satoh R Okubo S Kizawa H Komatsu H Matsumura F Noguchi Y Shinohara T Hinuma S Fujisawa Y Fujino M 《Nature》2003,422(6928):173-176
Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs. 相似文献
4.
Ishii H Kataura H Shiozawa H Yoshioka H Otsubo H Takayama Y Miyahara T Suzuki S Achiba Y Nakatake M Narimura T Higashiguchi M Shimada K Namatame H Taniguchi M 《Nature》2003,426(6966):540-544
The electronic transport properties of conventional three-dimensional metals are successfully described by Fermi-liquid theory. But when the dimensionality of such a system is reduced to one, the Fermi-liquid state becomes unstable to Coulomb interactions, and the conduction electrons should instead behave according to Tomonaga-Luttinger-liquid (TLL) theory. Such a state reveals itself through interaction-dependent anomalous exponents in the correlation functions, density of states and momentum distribution of the electrons. Metallic single-walled carbon nanotubes (SWNTs) are considered to be ideal one-dimensional systems for realizing TLL states. Indeed, the results of transport measurements on metal-SWNT and SWNT-SWNT junctions have been attributed to the effects of tunnelling into or between TLLs, although there remains some ambiguity in these interpretations. Direct observations of the electronic states in SWNTs are therefore needed to resolve these uncertainties. Here we report angle-integrated photoemission measurements of SWNTs. Our results reveal an oscillation in the pi-electron density of states owing to one-dimensional van Hove singularities, confirming the one-dimensional nature of the valence band. The spectral function and intensities at the Fermi level both exhibit power-law behaviour (with almost identical exponents) in good agreement with theoretical predictions for the TLL state in SWNTs. 相似文献
5.
Cell cycle progression by the repression of primary cilia formation in proliferating cells 总被引:1,自引:1,他引:0
Hidemasa Goto Akihito Inoko Masaki Inagaki 《Cellular and molecular life sciences : CMLS》2013,70(20):3893-3905
In most cell types, primary cilia protrude from the cell surface and act as major hubs for cell signaling, cell differentiation, and cell polarity. With the exception of some cells ciliated during cell proliferation, most cells begin to disassemble their primary cilia at cell cycle re-entry. Although the role of primary cilia disassembly on cell cycle progression is still under debate, recent data have emerged to support the idea that primary cilia exert influence on cell cycle progression. In this review, we emphasize a non-mitotic role of Aurora-A not only in the ciliary resorption at cell cycle re-entry but also in continuous suppression of cilia regeneration during cell proliferation. We also summarize recent new findings indicating that forced induction/suppression of primary cilia can affect cell cycle progression, in particular the transition from G0/G1 to S phase. In addition, we speculate how (de)ciliation affects cell cycle progression. 相似文献
6.
Masayuki Yamashita Yadav Navnath D. Masaki Nagahama Tomoki Inaba Ikuo Kawasaki Shunsaku Ohta 《复旦学报(自然科学版)》2005,44(5):895-896
1 Introduction Small ring size cycloalkanes such as cyclopropanes and cyclobutanes have been found as a basic structural constituent in a wide rang of natural products~([1]). In organic synthesis, their cycloalkanes also play an important role owing to their diversity of reaction.1IntroductionSmall ring size cycloalkanes such as cyclopropanes and cyclobutanes have beenfound as a basic structuralconstituent in a wide rang of natural products[1].In organic synthesis ,their cycloalkanes also pla… 相似文献
7.
This paper proposes an efficient framework to utilize quantum search practically.To the best of our knowledge,this is the first paper to show a concrete usage of quantum search in general programming.In our framework,we can utilize a quantum computer as a coprocessor to speed-up some parts of a program that runs on a classical computer.To do so,we propose several new ideas and techniques,such as a practical method to design a large quantum circuits for search problems and an efficient quantum comparator. 相似文献
8.
Elefteriou F Ahn JD Takeda S Starbuck M Yang X Liu X Kondo H Richards WG Bannon TW Noda M Clement K Vaisse C Karsenty G 《Nature》2005,434(7032):514-520
9.
通过采用go/no -go(应发出动作/不应发出动作)实验方法,在20世纪6 0-90年代末的不同期间,先后5次对中日两国儿童大脑神经活动类型(弱型、兴奋型、抑制 型、稳定型、活泼型)的调查发现:1)1984年中国儿童与1969年日本儿童大脑各类型的神 经活动出现率比较接近;2)中国1984年的调查与日本1979年的调查结果有明显差异;3)日 本1979年与1998年的调查结果相类似,而与中国1999年和1984年调查结果有较大变化. 对此 现象分析认为是儿童生活环境和生活方式发生巨大变化所致,最为明显的是:儿童在室外的 身体活动机会减少,儿童由以前的户外玩耍向室内看电视等比较静态的活动转移,儿童之间的交流减少. 相似文献
10.
HAR1 mediates systemic regulation of symbiotic organ development 总被引:35,自引:0,他引:35
Nishimura R Hayashi M Wu GJ Kouchi H Imaizumi-Anraku H Murakami Y Kawasaki S Akao S Ohmori M Nagasawa M Harada K Kawaguchi M 《Nature》2002,420(6914):426-429
Symbiotic root nodules are beneficial to leguminous host plants; however, excessive nodulation damages the host because it interferes with the distribution of nutrients in the plant. To keep a steady balance, the nodulation programme is regulated systemically in leguminous hosts. Leguminous mutants that have lost this ability display a hypernodulating phenotype. Through the use of reciprocal and self-grafting studies using Lotus japonicus hypernodulating mutants, har1 (also known as sym78), we show that the shoot genotype is responsible for the negative regulation of nodule development. A map-based cloning strategy revealed that HAR1 encodes a protein with a relative molecular mass of 108,000, which contains 21 leucine-rich repeats, a single transmembrane domain and serine/threonine kinase domains. The har1 mutant phenotype was rescued by transfection of the HAR1 gene. In a comparison of Arabidopsis receptor-like kinases, HAR1 showed the highest level of similarity with CLAVATA1 (CLV1). CLV1 negatively regulates formation of the shoot and floral meristems through cell-cell communication involving the CLV3 peptide. Identification of hypernodulation genes thus indicates that genes in leguminous plants bearing a close resemblance to CLV1 regulate nodule development systemically, by means of organ-organ communication. 相似文献