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Verónica Parrillas Laura Martínez-Muñoz Borja L. Holgado Amit Kumar Graciela Cascio Pilar Lucas José Miguel Rodríguez-Frade Marcos Malumbres Ana C. Carrera Karel HM van Wely Mario Mellado 《Cellular and molecular life sciences : CMLS》2013,70(3):545-558
Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma. 相似文献
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Blanco A Chomski E Grabtchak S Ibisate M John S Leonard SW Lopez C Meseguer F Miguez H Mondia JP Ozin GA Toader O van Driel HM 《Nature》2000,405(6785):437-440
Photonic technology, using light instead of electrons as the information carrier, is increasingly replacing electronics in communication and information management systems. Microscopic light manipulation, for this purpose, is achievable through photonic bandgap materials, a special class of photonic crystals in which three-dimensional, periodic dielectric constant variations controllably prohibit electromagnetic propagation throughout a specified frequency band. This can result in the localization of photons, thus providing a mechanism for controlling and inhibiting spontaneous light emission that can be exploited for photonic device fabrication. In fact, carefully engineered line defects could act as waveguides connecting photonic devices in all-optical microchips, and infiltration of the photonic material with suitable liquid crystals might produce photonic bandgap structures (and hence light-flow patterns) fully tunable by an externally applied voltage. However, the realization of this technology requires a strategy for the efficient synthesis of high-quality, large-scale photonic crystals with photonic bandgaps at micrometre and sub-micrometre wavelengths, and with rationally designed line and point defects for optical circuitry. Here we describe single crystals of silicon inverse opal with a complete three-dimensional photonic bandgap centred on 1.46 microm, produced by growing silicon inside the voids of an opal template of dose-packed silica spheres that are connected by small 'necks' formed during sintering, followed by removal of the silica template. The synthesis method is simple and inexpensive, yielding photonic crystals of pure silicon that are easily integrated with existing silicon-based microelectronics. 相似文献
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