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molecular Plant 2012年第5期5卷 993-1000页

作者： Xiu-Tang Wang Can Yuan Ting-Ting Yuan Su-Juan Cui Key laboratory of molecular cell biology in Hebei Province College of Life Science Hebei Normal University Shijiazhuang 050016 China

The anther is the male reproductive organ in flowering plants. Although some genes were reported to be involved in anther development, the molecular mechanisms underlying the transcriptional regulation of these genes is unclear. Ifr-2 （leaf and flower related-2）, the null allele of Arabidopsis thaliana LFR （LEAF AND FLOWER RELATED）, was male-sterile. The anthers of Ifr-2 plants were defective in sporogenous cell formation, tapetum development, and pollen development. In agreement with these phenotypes, expression studies showed that LFR was expressed in all cell layers of the anther, and that expression was particularly strong in the tapetal cells and pollen grains, Quantitative RT-PCR analysis revealed that LFR is required for the normal transcription of some anther development-related genes, such as AMS, CALS5, and DYT1, MS1 and MS2, and ROXY2. Genetic analysis showed that SPL was epistatic to LFR while LFR was epistatic to DYT1. We propose that LFR may be a crucial component in the regulation of a genetic network that modulates anther development.

关键词： cell differentiation/specialization gene expression gene regulation genetics reproductive biology Arabidopsis.

The coiled-coil domain containing protein Ccdc136b antagonizes maternal Wnt/β-catenin activity during zebrafish dorsoventral axial patterning

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Journal of Genetics and Genomics 2016年第7期43卷 431-438页

作者： Shi Wei Hanqiao Shang Yu Cao Qiang Wang State Key laboratory of Membrane biology CAS Center for Excellence in Molecular Cell ScienceInstitute of ZoologyChinese Academy of Sciences

The coiled-coil domain containing protein CCDC136 is a putative tumor suppressor and significantly down-regulated in gastric and colorectal cancer tissues. However, little is known about its biological functions during vertebrate embryo development. Zebrafish has two CCDC136 orthologs, ccdc136a and ccdc136b, but only ccdc136b is highly expressed during early embryonic development. In this study, we demonstrate that ccdc136b is required for dorsal-ventral axial patterning in zebrafish embryos, ccdc136b morphants display strongly dorsalized phenotypes. Loss- and gain-of-function experiments in zebrafish embryos and mammalian cells show that Ccdc136b is a crucial negative regulator of the Wnt/β-catenin signaling pathway, and plays a critical role in the establishment of the dorsal-ventral axis. We further find that Ccdc136b interacts with APC, promotes the binding affinity of APC withβ-catenin and then facilitates the turnover ofβ-catenin. These results provide the first evidence that CCDC136 regulates zebrafish dorsal-ventral patterning by antagonizing Wnt/β-catenin signal transduction and suggest a potential mechanism underlying its suppressive activity in carcinogenesis.

关键词： CCDC136 Dorsal-ventral patterning Wnt signaling β-catenin Zebrafish

Structural and biochemical studies of RIG-I antiviral signaling

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Protein & cell 2013年第2期4卷 142-154页

作者： Miao Feng Zhanyu Ding Liang Xu Liangliang Kong Wenjia Wang Shi Jiao Zhubing Shi Mark IGreene Yao Cong Zhaocai Zhou State Key laboratory of cell biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China State Key laboratory of molecular biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Department of Pathology and laboratory Medicine University of PennsylvaniaPA 19104USA

Retinoic acid-inducible gene I(RIG-I)is an important pattern recognition receptor that detects viral RNA and triggers the production of type-I interferons through the downstream adaptor MAVS(also called IPS-1,CARDIF,or VISA).A series of structural studies have elaborated some of the mechanisms of dsRNA recognition and activation of *** studies have proposed that K63-linked ubiquitination of,or unanchored K63-linked polyubiquitin binding to RIG-I positively regulates MAVS-mediated antiviral *** phos-phorylation of RIG-I appears to play an inhibitory role in controlling RIG-I antiviral signal *** we performed a combined structural and biochemical study to further define the regulatory features of RIG-I *** and dsRNA binding triggered dimeriza-tion of RIG-I with conformational rearrangements of the tandem CARD *** length RIG-I appeared to form a complex with dsRNA in a 2:2 molar ***-pared with the previously reported crystal structures of RIG-I in inactive state,our electron microscopic struc-ture of full length RIG-I in complex with blunt-ended dsRNA,for the first time,revealed an exposed active conformation of the CARD ***,we found that purified recombinant RIG-I proteins could bind to the CARD domain of MAVS independently of dsRNA,while S8E and T170E phosphorylation-mimick-ing mutants of RIG-I were defective in binding E3 ligase TRIM25,unanchored K63-linked polyubiquitin,and MAVS regardless of *** findings suggested that phosphorylation of RIG inhibited downstream signaling by impairing RIG-I binding with polyubiquitin and its interaction with MAVS.

关键词： RIG-I MAVS antiviral signaling polyubiq-uitin phosphorylation

Computational systems biology for omics data analysis

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Journal of molecular cell biology 2019年第8期11卷 631-632页

作者： Luonan Chen Key laboratory of Systems biology Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Shanghai 200031 China

Recent trend on biological data at a molecular level is omics data analysis for both bulk and single cells, in eluding genomics, proteomics, metabolomics, and epigenetics data (Wang and Zhang, 2017;Zhang et al., 2017;Zhao and Li, 2017;Cheng and Leung, 2018). Rapid accumulation of such high-dimensional biological data is driving the system-level study from describing complex phenomena to understanding molecular mechanisms (Park et al., 2018;Sun et al., 2018) and from analyzi ng in dividual components to understanding their networks and systems (Chen et al., 2009;Chen, 2017).

关键词： Computational systems biology omics data analysis

Microtubule-bundling protein Spef1 enables mammalian ciliary central apparatus formation

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Journal of molecular cell biology 2019年第1期11卷 67-77页

作者： Jianqun Zheng Hao Liu Lei Zhu Yawen Chen Huijie Zhao Wei Zhang Fan Li Lele Xie Xiumin Yan Xueliang Zhu State Key laboratory of cell biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Shanghai 200031China

Cilia are cellular protrusions containing nine microtubule(MT)doublets and function to propel cell movement or extracellular liquid flow through beating or sense environmental stimuli through signal *** require the central pair(CP)apparatus,consisting of two CP MTs covered with projections of CP proteins,for planar *** the CP MTs of such‘9+2’cilia are constructed,however,remains *** we identify Spef1,an evolutionarily conserved microtubule-bundling protein,as a core CP MT regulator in mammalian ***1 was selectively expressed in mammalian cells with 9+2 cilia and specifically localized along the *** depletion in multiciliated mouse ependymal cells by RNAi completely abolished the CP MTs and markedly attenuated ciliary localizations of CP proteins such as Hydin and Spag6,resulting in rotational beat of the ependymal ***1,which binds to MTs through its N-terminal *** domain,formed homodimers through its C-terminal coiled coil region to bundle and stabilize *** of either the MT-binding or the dimerization activity abolished the ability of exogenous Spef1 to restore the structure and functions of the CP *** propose that Spefl bundles and stabilizes central MTs to enable the assembly and functions of the CP apparatus.

关键词： central pair apparatus cilium microtubule mouse ependymal cell mouse tracheal epithelial cell Spef1

Vertebrate Dynein-f depends on Wdr78 for axonemal localization and is essential for ciliary beat

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Journal of molecular cell biology 2019年第5期11卷 383-394页

作者： Yirong Zhang Yawen Chen Jianqun Zheng Juan Wang Shichao Duan Wei Zhang Xiumin Yan Xueliang Zhu State Key laboratory of cell biology CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology University of Chinese Academy of Sciences Chinese Academy of Sciences 320 Yueyang Road Shanghai 200031 China

Motile cilia and flagella are microtubule-based organelles important for cell locomotion and extracellular liquid flow through beating. Although axonenal dyneins that drive ciliary beat have been extensively studied in unicellular Chlamydomonas, to what extent such knowledge can be applied to vertebrate is poorly known. In Chlamydomonas, Dynein-f controls flagellar waveforms but is dispensable for beating. The flagellar assembly of its heavy chains (HCs) requires its intermediate chain (IC) IC140 but not IC138. Here we show that, unlike its Chlamydomonas counte『part, vertebrate Dynein-f is essential for ciliary beat. We confirmed that Wdr78 is the vertebrate orthologue of IC3 Wdr78 associated with Dynein-f subunits such as Dnah2 (a HC) and Wdr63 (IC140 orthologue). It was expressed as a motile cilium-specific protein in mammalian cells. Depletion of Wdr78 or Dnah2 by RNAi paralyzed mouse ependymal cilia. Zebrafish Wdr78 morphants displayed ciliopathy-related phenotypes, such as curved bodies, hydrocephalus, abnormal otolith, randomized left-right asymmetry, and pronephric cysts, accompanied with paralyzed pronephric cilia. Furthermore, all the HCs and ICs of Dynein-f failed to localize in the Wdr78-depleted mouse ependymal cilia. Therefore, both the functions and subunit dependency of Dynein-fare altered in evolution, probably to comply with ciliary roles in higher organisms.

关键词： axonemal dynein Dynein-f IC138 motile cilium primary ciliary dyskinesia Wdr78 Dnah2

Gene expression profile favoring phenotypic reversion: a clue for mechanism of tumor suppression by NF-IL6 3'UTR

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cell Research 2003年第6期13卷 509-514页

作者： DING GAN LIU, QIU HONG JIANG, YUN Yl WEI, LI SUN, BEI BEI FU, Fu KUN ZHAO, QIONG ZHOU ’ State Key laboratory of molecular biology and Key laboratory of Proteomics, Institute of Biochemistryand cell biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai200031, China. E-mail: dgliu@*** State Key laboratory of molecular biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China Key laboratory of Proteomics Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Transfection of cDNA in 3’untranslated region of human nuclear factor for interleukin-6 (NF-IL6 3’UTR) induced tumor suppression in a human hepatoma cell line. cDNA array analysis was used to reveal changes in gene expression profile leading to tumor suppression The results indicate that this suppression was not due to activation of dsRNA-dependent protein kinase, nor to inactivation of oncogenes; rather, all the changes in expression of known genes, induced by NF-IL6 3’UTR cDNA may be ascribed to the suppression of cellular malignancy. Therefore, our results imply that this 3’untranslated region may have played role of a regulator of gene expression profile.

关键词： cDNA array NF-IL6 hepatoma 3 ’UTR tumor suppression.

p73β inhibits transcriptional activities of enhancer I and X promoter in hepatitis B virus more efficiently than p73α

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World Journal of Gastroenterology 2002年第6期8卷 1094-1097页

作者： Tsai-Ping Li State Key laboratory of molecular biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China

AIM: p73, as a novel member of a family of p53-related transcription factors, shares redundant functions with p53, such as the abilities of inducing apoptosis and suppressing growth. It is well known that p53 can repress HBV expression and transcription efficiently. The aim of this paper is to investigate the transcriptional effect of p73α and p73β on hepatitis B virus (HBV) and to understand the correlation between HBV and ***: To construct an x-gene inactivated HBV plasmid which was cotransfected with p73α or p73β expression vectors into HepG2 cells. After transiently transfecticn, HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) were detected by ELISA. Viral transcripts synthesized by HBV were evaluated by Northern blotting analysis. The activities of HBV regulatory elements, including enhancer Ⅰ/X promoter (ENI/Xp) and enhancer Ⅱ/core promoter (ENⅡ/Cp) were monitored by luciferase ***: Both p73α and p73β could repress HBsAg and HBeAg expression by downregulating the ENⅠ/Xp and ENⅡ/Cp activities. But p73β exerted stronger inhibition on the activity of ENI/Xp than p73α, resulting in much lower level of viral transcripts and the antigens ***: p73β as a novel member of p53 family can efficiently inhibit HBV transcription mainly through downregulating the activities of the HBV ENI/Xp regulatory elements.

关键词： B肝病毒 I增强子 X启动子转录活性 p73β 抑制作用 p73α

Generation of genetically modified mice using CRISPR/Cas9 and haploid embryonic stem cell systems

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Zoological Research 2016年第4期37卷 205-213页

作者： Li-Fang JIN Jin-Song LI College of Life Science of Shaoxing University Shaoxing Zhejiang 312000 China State Key laboratory of cell biology CAS Center for Excellence in Molecular Cell Science Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Science Shanghai 200031 China Shanghai Key laboratory of molecular Andrology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological SciencesChinese Academy of Science Shanghai 200031 China

With the development of high-throughput sequencing technology in the post-genomic era, researchers have concentrated their efforts on elucidating the relationships between genes and their corresponding functions. Recently, important progress has been achieved in the generation of genetically modified mice based on CRISPR/Cas9 and haploid embryonic stem cell （haESC） approaches, which provide new platforms for gene function analysis, human disease modeling, and gene therapy. Here, we review the CRISPR/Cas9 and haESC technology for the generation of genetically modified mice and discuss the key challenges in the application of these approaches.

关键词： CRISPR/Cas9 Haploid embryonic stem cells Mouse Genetic modification

Connecting Calcium-Based Nanomaterials and Cancer:From Diagnosis to Therapy

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Nano-Micro Letters 2022年第9期14卷 95-131页

作者： Shuang Bai Yulu Lan Shiying Fu Hongwei Cheng Zhixiang Lu Gang Liu State Key laboratory of molecular Vaccinology and molecular Diagnostics Center for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102People’s Republic of China State Key laboratory of cellular Stress biology Innovation Center for Cell BiologySchool of Life SciencesXiamen UniversityXiamen 361102

As the indispensable second cellular messenger,calcium signaling is involved in the regulation of almost all physiological processes by activating specific target *** importance of calcium ions(Ca^(2+))makes its“Janus nature”strictly regulated by its *** regulation of calcium signals may cause some diseases;however,artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role.“Calcium overload,”for example,is characterized by excessive enrichment of intracellular Ca^(2+),which irreversibly switches calcium signaling from“positive regulation”to“reverse destruction,”leading to cell ***,this undesirable death could be defined as“calcicoptosis”to offer a novel approach for cancer ***,Ca^(2+)is involved in various cancer diagnostic and therapeutic events,including calcium overload-induced calcium homeostasis disorder,calcium channels dysregulation,mitochondrial dysfunction,calcium-associated immunoregulation,cell/vascular/tumor calcification,and calcification-mediated CT *** paral-lel,the development of multifunctional calcium-based nanomaterials(e.g.,calcium phosphate,calcium carbonate,calcium peroxide,and hydroxyapatite)is becoming abundantly *** review will highlight the latest insights of the calcium-based nanomaterials,explain their application,and provide novel *** and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.

关键词： Calcium-based nanomaterials Cancer therapy Calcium signaling Tumor calcification Theranostics