Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53

Aurora kinase A (also called STK15 and BTAK) is overexpressed in many human cancers. Ectopic overexpression of aurora kinase A in mammalian cells induces centrosome amplification, chromosome instability and oncogenic transformation, a phenotype characteristic of loss-of-function mutations of p53. Here we show that aurora kinase A phosphorylates p53 at Ser315, leading to its ubiquitination by Mdm2 and proteolysis. p53 is not degraded in the presence of inactive aurora kinase A or ubiquitination-defective Mdm2. Destabilization of p53 by aurora kinase A is abrogated in the presence of mutant Mdm2 that is unable to bind p53 and after repression of Mdm2 by RNA interference. Silencing of aurora kinase A results in less phosphorylation of p53 at Ser315, greater stability of p53 and cell-cycle arrest at G2-M. Cells depleted of aurora kinase A are more sensitive to cisplatin-induced apoptosis, and elevated expression of aurora kinase A abolishes this response. In a sample of bladder tumors with wild-type p53, elevated expression of aurora kinase A was correlated with low p53 concentration. We conclude that aurora kinase A is a key regulatory component of the p53 pathway and that overexpression of aurora kinase A leads to increased degradation of p53, causing downregulation of checkpoint-response pathways and facilitating oncogenic transformation of cells.     

Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development

Receptor tyrosine kinases often have critical roles in particular cell lineages by initiating signalling cascades in those lineages. Examples include the neural-specific TRK receptors, the VEGF and angiopoietin endothelial-specific receptors, and the muscle-specific MUSK receptor. Many lineage-restricted receptor tyrosine kinases were initially identified as 'orphans' homologous to known receptors, and only subsequently used to identify their unknown growth factors. Some receptor-tyrosine-kinase-like orphans still lack identified ligands as well as biological roles. Here we characterize one such orphan, encoded by Ror2 (ref. 12). We report that disruption of mouse Ror2 leads to profound skeletal abnormalities, with essentially all endochondrally derived bones foreshortened or misshapen, albeit to differing degrees. Further, we find that Ror2 is selectively expressed in the chondrocytes of all developing cartilage anlagen, where it essential during initial growth and patterning, as well as subsequently in the proliferating chondrocytes of mature growth plates, where it is required for normal expansion. Thus, Ror2 encodes a receptor-like tyrosine kinase that is selectively expressed in, and particularly important for, the chondrocyte lineage.     

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution

Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages.     

纸质图书与网络阅读现状思考

纸质阅读作为一种历史悠久的传统阅读方式,一直是阅读的主流,但是近十年来,随着计算机和互联网的兴起,网络阅读以一种全新的阅读方式出现在人们的生活中.尤其是大屏幕智能手机和平板电脑等移动终端的大量普及,网络阅读发展势头迅猛,似乎有超越纸质阅读的势头.本文从纸质图书与网络阅读的特性出发,来探究二者的发展.     

链格孢属真菌对农作物的危害

链格孢属(Altemaria)真菌是农作物的主要致病菌之一,它能引起包括玉米、小麦、烟草、马铃薯、番茄、苹果、梨等几十种农作物发病,其发病机理主要是由病菌的代谢产物——毒素导致的,由于毒素的作用使农作物产生各种症状,如黑斑病、褐斑病、茎枯病、赤星病等等,严重影响了农作物的产量,给我国农业生产带来了巨大损失。     

蜂蜜、蜂王浆的真伪鉴别

在现代的快节奏生活中，人们的自我保健意识越来越强，食用保健食品为一种常用方式。蜂蜜、蜂王浆是纯天然保健食品中的该饮者，它们良好的保健作用已被越来越多的消费者认可，市场也越来越大，由上它们营养价值高，产量少，价格白然也就较高，同而出现有冷目混珠的假蜂蜜、假蜂王浆牟取高利坑害消费者的行为。现总结出些鉴别真伪的方法。l蜂蜜的真伪鉴别天然蜂蜜是蜜蜂采集植物蜜腺的分泌物，经蜜蜂充分酿造而成，它味极甜，有明显的花香味。制造假蜂蜜大致有以下几种方法：门）白砂糖熬制；门）治糖或采葡糖浆；（3）由甜味素、色素、香精…