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Sebastian Kalamajski Dominique Bihan Arkadiusz Bonna Kristofer Rubin Richard W. Farndale 《The Journal of biological chemistry》2016,291(15):7951-7960
The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites. 相似文献
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A. Tchirkov Jacques-Olivier Bay David Pernin Yves-Jean Bignon Pascale Rio Maria Grancho Fabrice Kwiatkowski Michel Giollant Paul Malet Pierre Verrelle 《Human genetics》1997,101(3):312-316
In ataxia-telangiectasia (A-T) patients, mutations in a single gene, ATM, result in an autosomal recessive syndrome that embraces a variety of clinical features and manifests extreme radiosensitivity
and a strong predisposition to malignancy. Heterozygotes for the ATM gene have no clinical expression of A-T but may be cancer prone with a moderate increase in in vitro radiosensitivity. We
performed a blind chromosomal analysis on G2-phase lymphocytes from 7 unrelated A-T patients, 13 obligate A-T heterozygotes (parents of the patients), and 14 normal controls
following X-irradiation with 1 Gy in order to evaluate this cytogenetic method as a tool for detection of ATM carriers. Both A-T homozygotes and heterozygotes showed significantly increased levels of radiation-induced chromatid damage
relative to that of normal controls. These results show that the G2-phase chromosomal radiosensitivity assay can be used for the detection of A-T heterozygotes. In combination with molecular
genetic analyses, this test may be of value in studies of familial and sporadic cancers aimed at determination of the potential
involvement of ATM mutations in tumor risk or development.
Received: 5 May 1997 / Accepted: 26 August 1997 相似文献
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Gecko phylogeography in the Western Indian Ocean region: the oldest clade of Ebenavia inunguis lives on the youngest island 下载免费PDF全文
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Schuster Martina Tewary Gargi Bao Xuanwen Subedi Prabal Hauck Stefanie M. Olsen Ann Karin Eide Dag Markus Trott Klaus Rüdiger Götz Sebastian Atkinson Michael J. Rosemann Michael 《Radiation and environmental biophysics》2021,60(4):689-689
Radiation and Environmental Biophysics - 相似文献
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Hartmut Heller Sebastian Brandt Klaus-Dieter Schuster 《Journal of applied physiology》2002,92(4):1770; author reply 1770-1770; author reply 1771