Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation

Meiosis is a specialized cell division in which two chromosome segregation phases follow a single DNA replication phase. The budding yeast Polo-like kinase Cdc5 was found to be instrumental in establishing the meiosis I chromosome segregation program. Cdc5 was required to phosphorylate and remove meiotic cohesin from chromosomes. Furthermore, in the absence of CDC5 kinetochores were bioriented during meiosis I, and Mam1, a protein essential for coorientation, failed to associate with kinetochores. Thus, sister-kinetochore coorientation and chromosome segregation during meiosis I are coupled through their dependence on CDC5.     

Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1

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.     

Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE

The cytokine tumor necrosis factor (TNF) is the primary trigger of inflammation. Like many extracellular signaling proteins, TNF is synthesized as a transmembrane protein; the active signal is its ectodomain, which is shed from cells after cleavage by an ADAM family metalloprotease, ADAM17 (TNFα-converting enzyme, TACE). We report that iRhom2 (RHBDF2), a proteolytically inactive member of the rhomboid family, is required for TNF release in mice. iRhom2 binds TACE and promotes its exit from the endoplasmic reticulum. The failure of TACE to exit the endoplasmic reticulum in the absence of iRhom2 prevents the furin-mediated maturation and trafficking of TACE to the cell surface, the site of TNF cleavage. Given the role of TNF in autoimmune and inflammatory diseases, iRhom2 may represent an attractive therapeutic target.     

Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex

The complex containing the Mre11, Rad50, and Nbs1 proteins (MRN) is essential for the cellular response to DNA double-strand breaks, integrating DNA repair with the activation of checkpoint signaling through the protein kinase ATM (ataxia telangiectasia mutated). We demonstrate that MRN stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX. MRN makes multiple contacts with ATM and appears to stimulate ATM activity by facilitating the stable binding of substrates. Phosphorylation of Nbs1 is critical for MRN stimulation of ATM activity toward Chk2, but not p53. Kinase-deficient ATM inhibits wild-type ATM phosphorylation of Chk2, consistent with the dominant-negative effect of kinase-deficient ATM in vivo.     

Protein kinase C and regulation of the local competence of Xenopus ectoderm

The limited competence of embryonic tissue to respond to an inductive signal has an essential, regulatory function in embryonic induction. The molecular basis for the competence of Xenopus ectoderm to differentiate into neural tissue was investigated. Dorsal mesoderm or 12-O-tetradecanoyl phorbol-13-acetate (TPA) caused in vivo activation of protein kinase C (PKC) and neural differentiation mainly in dorsal ectoderm and to a lesser extent in ventral ectoderm. These data correlate with the observations that PKC preparations from dorsal and ventral ectoderm differ, the dorsal PKC preparation being more susceptible to activation by TPA and diolein than is the ventral PKC preparation. Monoclonal antibodies against the bovine PKC alpha plus beta or gamma isozymes immunostained dorsal and ventral ectoderm, respectively, which suggests different localizations of PKC isozymes. These results suggest that PKC participates in the establishment of embryonic competence.     

关于以信息推动农业发展的探索

以信息化推动农业的发展是社会经济发展的必然趋势,实现农业信息化是发展现代农业的重要内容,是推动现代农业进程的有效手段,是改变农业面貌主要途径.     

谈如何大力推进生态文化建设

生态文化是关于人与自然和谐相处、协同发展的文化。生态文化在建设中国特色社会主义现代化进程中具有重要意义。要坚持普遍性和特殊性相结合、总体性和重点性相结合、理论性和实践性相结合、传统性和时代性相结合的原则,针对目前我国生态文化的发展现状和存在问题,从组织、法制、政策、社会、科技、人才等多个路径入手,大力推进生态文化建设。     

培训教育数字化校园建设信息化

干部培训类院校是培养领导干部和公务员的学校。研究发现,新时期领导干部和公务员培训出现了一些新情况和新特点。为了适应干部培训的新需要,我们吉林省委党校进行了较系统的数字化建设。     

加快推行农业标准化的几点建议

农业标准化包括种植业、林业、畜牧业、渔业、农用微生物业的标准化 ,它是指按照“统一、简化、协调、优选”的原理 ,通过制定标准和实施标准 ,把农业生产的产前、产中、产后全过程纳入标准化生产和标准化管理轨道的活动。农业标准是实现农业现代化的重要基础 ,农业标准化是提高我国农业生产效率和农产品质量 ,应对“入世”挑战的有力武器。我国要提升农业产业经济地位 ,增加农民收入 ,在国际农产品及食品贸易市场抢占一席之地 ,必须大力推行农业标准化。那么如何加快农业标准化进程 ,全面提高农产品质量 ,笔者认为应做好以下几方面工作。1…     

浅谈如何运用交际性原则促进大学英语教学

本文从教师与学生,学生与学生及学生与作者三个方面,探讨如何在大学英语教学当中充分运用交际性原则,更好的促进大学英语教学。     

An ATP gate controls tubulin binding by the tethered head of kinesin-1

Kinesin-1 is a two-headed molecular motor that walks along microtubules, with each step gated by adenosine triphosphate (ATP) binding. Existing models for the gating mechanism propose a role for the microtubule lattice. We show that unpolymerized tubulin binds to kinesin-1, causing tubulin-activated release of adenosine diphosphate (ADP). With no added nucleotide, each kinesin-1 dimer binds one tubulin heterodimer. In adenylyl-imidodiphosphate (AMP-PNP), a nonhydrolyzable ATP analog, each kinesin-1 dimer binds two tubulin heterodimers. The data reveal an ATP gate that operates independently of the microtubule lattice, by ATP-dependent release of a steric or allosteric block on the tubulin binding site of the tethered kinesin-ADP head.     

加强基地建设,促进重点学科可持续发展

本介绍了基地建设的涵义，剖析了基地建设的三要素：队伍建设、条件建设和运行机制。阐述了基地对学科创新、学科整合以及促进产学研结合等方面的依托作用，提出了加强基地建设是提高重点学科可持续发展能力的有效途径。     

加强人文素质教育促进学生全面自由发展

加强人文素质教育是世界范围内高等教育发展的趋势。通过对加强人文素质教育重要性的阐述，对原因、目的、现状及措施等方面的剖析，认为加强人文素质教育是提高学生综合能力，培养学生个性发展的重要途径。     

Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. Genetic analysis of AMPK or ULK1 in mammalian liver and Caenorhabditis elegans revealed a requirement for these kinases in autophagy. In mammals, loss of AMPK or ULK1 resulted in aberrant accumulation of the autophagy adaptor p62 and defective mitophagy. Reconstitution of ULK1-deficient cells with a mutant ULK1 that cannot be phosphorylated by AMPK revealed that such phosphorylation is required for mitochondrial homeostasis and cell survival during starvation. These findings uncover a conserved biochemical mechanism coupling nutrient status with autophagy and cell survival.     

Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation

Cells reuse signaling proteins in multiple pathways, raising the potential for improper cross talk. Scaffold proteins are thought to insulate against such miscommunication by sequestering proteins into distinct physical complexes. We show that the scaffold protein Ste5, which organizes the yeast mating mitogen-activated protein kinase (MAPK) pathway, does not use sequestration to prevent misactivation of the mating response. Instead, Ste5 appears to use a conformation mechanism: Under basal conditions, an intramolecular interaction of the pleckstrin homology (PH) domain with the von Willebrand type A (VWA) domain blocks the ability to coactivate the mating-specific MAPK Fus3. Pheromone-induced membrane binding of Ste5 triggers release of this autoinhibition. Thus, in addition to serving as a conduit guiding kinase communication, Ste5 directly receives input information to decide if and when signal can be transmitted to mating output.