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Lysozyme-Cre-mediated conditional deletion of UBA3 augments endotoxin shock

Lysozyme-Cre-mediated conditional deletion of UBA3 augments ...

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第九届全国免疫学学术大会

作者：张雪莹叶珍洁裴钰君张纪岩军事医学科学院基础医学研究所

Ubiquitin-like proteins NEDD8 is covalently attached to lysines in substrate proteins by a series of enzymatic reactionssimilar to those involved in ubiquitination including the E1(NAE1/UBA3)*** well-characterized substrates of NEDD8 modification(officially named as neddylation)are *** of NF-kappa B,a transcription factor required for the inducible expression of various proinflammatory cytokines,occurs through phosphorylation-dependent ubiquitination of IkappaB alpha,which is subsequently degraded by the 26S *** has been demonstrated that IkappaBalpha ubiquitination is carried out by a ubiquitin-ligase enzyme called ***8 modification of the Cullin-1 component of SCFhas been revealed to be essential for the function of SCFin IkappaBalpha ***,it has been found that blockade of neddylation represses LPS-induced production of proinflammatory cytokines from ***,it has been suggested that the neddylation pathway could be targeted to alleviate the inflammatory ***,the role of neddylation in mammalian physiology remains *** homozygous for a UBA3 conditional allele were backcrossed to the C57 BL/6J strain and were then crossed with mice expressing a transgene encoding Cre recombinase driven by the murine M lysozyme promoter(LysM-Cre mice).Unexpectedly,UBA3mice were found to be more sensitive to LPS challenge than littermate *** revealed that the increase IL-10 levels in the serum of UBA3mice after LPS challenge was ***,the increase of the levels of IL-6,IL-1beta,and TNF-alpha was *** unexpected data promoted us to further explore the possible underlying ***3mice exhibited normal percentages of CD11b+F4/80+and CD11bGr1cells in the peripheral blood,spleen,and bone ***-marrow derived macrophages from UBA3mice showed unaffected activation of IKK,ERK,JNK,and p38 in response to ***,the degradation of IkappaBalpha was a

关键词： UBA3 neddylatin endotoxin shock

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