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排序方式: 共有830条查询结果,搜索用时 15 毫秒
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Preckel T Fung-Leung WP Cai Z Vitiello A Salter-Cid L Winqvist O Wolfe TG Von Herrath M Angulo A Ghazal P Lee JD Fourie AM Wu Y Pang J Ngo K Peterson PA Früh K Yang Y 《Science (New York, N.Y.)》1999,286(5447):2162-2165
In vitro PA28 binds and activates proteasomes. It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in PA28-/- mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses. 相似文献
54.
Lopatto D Alvarez C Barnard D Chandrasekaran C Chung HM Du C Eckdahl T Goodman AL Hauser C Jones CJ Kopp OR Kuleck GA McNeil G Morris R Myka JL Nagengast A Overvoorde PJ Poet JL Reed K Regisford G Revie D Rosenwald A Saville K Shaw M Skuse GR Smith C Smith M Spratt M Stamm J Thompson JS Wilson BA Witkowski C Youngblom J Leung W Shaffer CD Buhler J Mardis E Elgin SC 《Science (New York, N.Y.)》2008,322(5902):684-685
55.
Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1 总被引:2,自引:0,他引:2
Urano F Wang X Bertolotti A Zhang Y Chung P Harding HP Ron D 《Science (New York, N.Y.)》2000,287(5453):664-666
Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha-/- fibroblasts were impaired in JNK activation by ER stress. The cytoplasmic part of IRE1 bound TRAF2, an adaptor protein that couples plasma membrane receptors to JNK activation. Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals. 相似文献
56.
Mao JH Kim IJ Wu D Climent J Kang HC DelRosario R Balmain A 《Science (New York, N.Y.)》2008,321(5895):1499-1502
The enzyme mTOR (mammalian target of rapamycin) is a major target for therapeutic intervention to treat many human diseases, including cancer, but very little is known about the processes that control levels of mTOR protein. Here, we show that mTOR is targeted for ubiquitination and consequent degradation by binding to the tumor suppressor protein FBXW7. Human breast cancer cell lines and primary tumors showed a reciprocal relation between loss of FBXW7 and deletion or mutation of PTEN (phosphatase and tensin homolog), which also activates mTOR. Tumor cell lines harboring deletions or mutations in FBXW7 are particularly sensitive to rapamycin treatment, which suggests that loss of FBXW7 may be a biomarker for human cancers susceptible to treatment with inhibitors of the mTOR pathway. 相似文献
57.
Steed PM Tansey MG Zalevsky J Zhukovsky EA Desjarlais JR Szymkowski DE Abbott C Carmichael D Chan C Cherry L Cheung P Chirino AJ Chung HH Doberstein SK Eivazi A Filikov AV Gao SX Hubert RS Hwang M Hyun L Kashi S Kim A Kim E Kung J Martinez SP Muchhal US Nguyen DH O'Brien C O'Keefe D Singer K Vafa O Vielmetter J Yoder SC Dahiyat BI 《Science (New York, N.Y.)》2003,301(5641):1895-1898
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands. 相似文献
58.
Lanza R Chung Y West MD Campbell KH 《Science (New York, N.Y.)》2003,301(5639):1482; author reply 1482
59.
试论呼市地区园林植物五小害虫的发展状况和防治策略 总被引:1,自引:0,他引:1
本文在实地调查和试验研究的基础上,系统地分析了呼市地区园林植物五小害虫的发展状况,在初步查清主要危害虫种及其生物学特性基础上,提出了加强植物检疫,利用,保护天敌,加强生物防治的研究,适时采用物理防治方法,合理科学地应用化学防治法的综合防治策略,对化学杀虫剂的选择,使用浓度,施药时间和次数提出了科学有效的试验依据。 相似文献
60.
Guidotti LG Rochford R Chung J Shapiro M Purcell R Chisari FV 《Science (New York, N.Y.)》1999,284(5415):825-829
Viral clearance during hepatitis B virus (HBV) infection has been thought to reflect the destruction of infected hepatocytes by CD8(+) T lymphocytes. However, in this study, HBV DNA was shown to largely disappear from the liver and the blood of acutely infected chimpanzees long before the peak of T cell infiltration and most of the liver disease. These results demonstrate that noncytopathic antiviral mechanisms contribute to viral clearance during acute viral hepatitis by purging HBV replicative intermediates from the cytoplasm and covalently closed circular viral DNA from the nucleus of infected cells. 相似文献