DNA damage stress induces the dissociation of Smurf1/2 from MDM2 in a slow manner

The tumor suppressor p53 locates at the key point of cell growth or apoptosis balance, and the expression level of p53 is tightly controlled by ubiquitin ligases including MDM2. Upon DNA damage stresses, p53 was accumulated and activated, leading to cell cycle arrest or apoptosis. We previously showed that Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by interacting with and stabilizing MDM2, and consequently enhancing MDM2-mediated ubiquitylation of p53. However, it is unclear how the Smurf1-MDM2 interaction is regulated in response to DNA damage stress. Here, we show that in response to etoposide treatment Smurf1 dissociates from MDM2, resulting in MDM2 destabilization and p53 accumulation. The negative regulation of Smurf1 on apoptosis is released. Notably, this dissociation is a slow process rather than a rapid response, implicating high expression of Smurf1 might confer the resistance against p53 activation. Consistent with this notion, we observed that Smurf1/2 ligases are highly expressed in colon cancer, esophageal squamous cell carcinoma and pancreatic cancer tissues, suggesting the oncogenic tendency of Smurf1/2.     

Variations of geochemical compositions and the paleoclimatic significance of a loess-soil sequence from Garzê County of western Sichuan Province, China

The West Sichuan Plateau is located in the southeast margin of the Tibetan Plateau, where the climate is mainly influenced by the Indian southwest summer monsoon and the Tibetan Plateau monsoon. In this study, detailed geochemical analysis has been carried out on Ganzisi loess-paleosol sequence in Ganzê County of western Sichuan Province. The results indicate that Ganzê loess and paleosol have experienced the incipient stage of chemical weathering in dust source regions, characterized by the decomposition of plagioclase which caused the depletion of mobile elements Na and Ca. The post-depositional chemical weathering is characterized by carbonate dissolution and oxidation of Fe2＋. The variations of some geochemical indexes （such as CIA values, Na/K and Fe2＋/ Fe3＋ ratios） in Ganzisi loess-paleosol sequence indicate a gradually decreased chemical weathering intensity in the dust source regions and deposition areas since 1.15 Ma BP consistent with the general increase of global ice volume, reflecting that the arid trend since 1.15 Ma BP in the southeast Tibetan Plateau is a regional response to the global climate change. The geochemical indexes in this section also reveal an obvious drying step occurred at about 250 ka BP in this region. We interpret this drying step as a result of decreased influence of the Indian southwest summer monsoon. This decrease in monsoon moisture is probably attributable to the uplift of the southeast margin of the Tibetan Plateau at about 250 ka BP.     

巨噬细胞极性及调控机制

巨噬细胞是具有异质性的一群免疫细胞,在病原微生物和组织损伤所引起的炎症反应及消解过程中发挥关键作用.不同的诱导信号可激活巨噬细胞改变其自身的形态和生理特征,表现出显著的可塑性来应对外界环境.借用辅助性T细胞(Th)的概念,从激活方式上将巨噬细胞分为经典激活的巨噬细胞(classically activated macrophages,CAMs或M1)和非经典激活的巨噬细胞(alternatively activated macrophages,AAMs或M2)两大类.M1型巨噬细胞产生促炎症细胞因子,抵抗病原入侵但也造成机体损伤;M2型分泌抗炎症细胞因子,并在组织修复与重建和肿瘤的形成过程中发挥作用.本文介绍了巨噬细胞的激活机制和巨噬细胞极性的关系,重点总结了近年来巨噬细胞极性调控机制方面的最新研究进展,并分析预测了该领域的发展趋势.