Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human dise...Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.展开更多
During cell division,chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere.Accurate attachment of spindle microtubules to kinetochore requires the chromosomal passenger ...During cell division,chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere.Accurate attachment of spindle microtubules to kinetochore requires the chromosomal passenger of Aurora B kinase complex with borealin,INCENP and survivin(SUR).The current working model argues that SUR is responsible for docking Aurora B to the centromere whereas its precise role in Aurora B activation has been unclear.Here,we show that Aurora B kinase activation requires SUR priming phosphorylation at Ser20 which is catalyzed by polo-like kinase 1(PLK1).Inhibition of PLK1 kinase activity or expression of non-phosphorylatable SUR mutant prevents Aurora B activation and correct spindle microtubule attachment.The PLK1-mediated regulation of Aurora B kinase activity was examined in real-time mitosis using fluorescence resonance energy transfer-based reporter and quantitative analysis of native Aurora B substrate phosphorylation.We reason that the PLK1-mediated priming phosphorylation is critical for orchestrating Aurora B activity in centromere which is essential for accurate chromosome segregation and faithful completion of cytokinesis.展开更多
Kinesin superfamily of microtubule- based motor orchestrates a variety of cellular proc- esses. Recent availability of mammalian genomes has enabled analyses of kinesins on the whole ge- nome. Here we present a novel ...Kinesin superfamily of microtubule- based motor orchestrates a variety of cellular proc- esses. Recent availability of mammalian genomes has enabled analyses of kinesins on the whole ge- nome. Here we present a novel full-length kinesin prediction program (FKPP) for mammalian kinesin gene discovery based on a comparative genomics approach. Contrary to previous predictions of 94 kinesins, we identify a total of 134 potentially kinesin genes from mammalian genomes, including 45 from mouse, 45 from rat and 44 from human. In addition, FKPP synthesizes 25 potentially full-length mam- malian kinesins based on the partial sequences in the database. Surprisingly, FKPP reveals that full-length human CENP-E contains 2701 aa rather than 2663 aa in the database. Experimentation using sequence specific antibody and cDNA sequencing of human CENP-E validates the accuracy of FKPP. Given the remarkable computing efficiency and accuracy of FKPP, we reclassify the mammalian kinesin super- family. Since current databases contain many in- complete sequences, FKPP may provide a novel approach for molecular delineation of kinesins and other protein families.展开更多
Endoplasmic reticulum(ER)stress is involved in ischemic preconditioning that protects various organs from ischemia/reperfusion(I/R)injury.We established an in vivo ER stress preconditioning model in which tunicamycin ...Endoplasmic reticulum(ER)stress is involved in ischemic preconditioning that protects various organs from ischemia/reperfusion(I/R)injury.We established an in vivo ER stress preconditioning model in which tunicamycin was injected into rats before hepatic I/R.The hepatic I/R injury,demonstrated by serum aminotransferase level and the ultra-structure of the liver,was alleviated by administration of tunicamycin,which induced ER stress in rat liver by activating inositol-requiring enzyme1(IRE1)andupregulating78 kDaglucose-regulated protein(GRP78).The proteomic identification for IRE1 binders revealed interaction and cooperation among receptor for activated C kinase 1(RACK1),phosphorylated AMPK,and IRE1 under ER stress conditions in a spatiotemporal manner.Furthermore,in vitro ER stress preconditioningwas induced by thapsigargin and tunicamycin in L02 and Hep G2 cells.Surprisingly,BCL2 was found to bephosphorylated by IRE1 under ER stress conditions to prevent apoptotic process by activation of autophagy.In conclusion,ER stress preconditioning protects against hepatic I/R injury,which is orchestrated by IRE1-RACK1 axis through the activation of BCL2.Our findings provide novel insights into the molecular pathways underlying ER stress preconditioning-elicited cytoprotective effect against hepatic I/R injury.展开更多
基金We thank members of our group for insightful discussion during the course of this study.This work was supported by grants from Chinese Academy of Science(KSCX1-YW-R65,KSCX2-YW-H10)National Basic Research Program of China(2002CB713700)+4 种基金Hi-Tech Research and Development Program of China(2001AA215331)Chinese Minister of Education(20020358051 to XY,PCSIRT0413 to XD)National Natural Science Foundation of China(39925018,30270293 to XY,30500183 to XD,30600222 to JY)National Institutes of Health(USA)(DK56292,CA92080)to XY(a Georgia Cancer Coalition Eminent Scholar)JY was supported by China Postdoctor(2005037560).
基金National Natural Science Foundation of China （39925018, 90508002 , 30121001） Chinese Academy of Science （KSCX 1-R65 and RSCX2-H10）+2 种基金 National Basic Research Program of China （973 project, 2002CB713700） American Cancer Society （RPG-99-173-01） a Gcc Breast Cancer Research award and National Institutes of Health grants DK56292 and CA89019 to XY （a GCC Eminent Scholar） and NS36194 （JW）.
基金supported by the National Natural Science Foundation of China(31871380,32000500,32070730,32170756,32170804,81330008,81671377,81725010,81725010,81872874,81921006,81922027,81971312,81991512,82030041,82103167,82122024,82125009,82125011,82130044,91749126,91949101,91949207,92049302)the National Key Research and Development Program of China(2017YFA0506400,2018YFA0800200,2018YFA0800700,2018YFA0900200,2018YFC2000100,2018YFC2000400,2018YFE-0203700,20192ACB70002,2019YFA0802202,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002800,2020YFC-2002900,2021ZD0202401)+11 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100,XDA16010603,XDA16020400,XDB29020000,XDB39000000,XDB39000000,XDB39030300)the China Association for Science and Technology(2021QNRC001)the Beijing Municipal Science and Technology Commission(Z200022)the Natural Science Foundation of Shanghai(21JC1406400)the Key Programs of the Jiangxi ProvinceChina(20192ACB70002)the“Shu Guang”Project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation(19SG18)the Shanghai Sailing Program(22YF1434300)the Research Project of Joint Laboratory of University of Science and Technology of China and Anhui Mental Health Center(2019LH03)the Fundamental Research Funds for the Central Universities(WK2070210004)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(YESS20210002)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022083)。
文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.
基金supported,in whole or in part,by National Institutes of Health(NIH)Grants DK-56292 and CA132389 and NIH,National Center for Research Resources(NCRR),Grant UL1 RR025008 from the Clinical and Translational Science Award Programsupported by Chinese Natural Science Foundation Grants 30500183 and 30870990(to X.D.),and 90508002 and 90913016(to X.Y.)+5 种基金Chinese Academy of Science Grants KSCX1-YW-R-65,KSCX2-YW-H-10,KSCX2-YW-R-195the Major State Basic Research Development Program of China(973 Program)2007CB914503 and 2010CB912103International Collaboration Grant 2009DFA31010(to X.D.)and Technology Grant 2006BAI08B01-07(to X.D.)a Georgia Cancer Coalition Breast Cancer Research GrantAtlanta Clinical and Translational Science Award Chemical Biology Grant P20RR011104 and Anhui Province Key Project Grant,08040102005supported in part by NCRR,NIH,Grant G12RR03034.
文摘During cell division,chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere.Accurate attachment of spindle microtubules to kinetochore requires the chromosomal passenger of Aurora B kinase complex with borealin,INCENP and survivin(SUR).The current working model argues that SUR is responsible for docking Aurora B to the centromere whereas its precise role in Aurora B activation has been unclear.Here,we show that Aurora B kinase activation requires SUR priming phosphorylation at Ser20 which is catalyzed by polo-like kinase 1(PLK1).Inhibition of PLK1 kinase activity or expression of non-phosphorylatable SUR mutant prevents Aurora B activation and correct spindle microtubule attachment.The PLK1-mediated regulation of Aurora B kinase activity was examined in real-time mitosis using fluorescence resonance energy transfer-based reporter and quantitative analysis of native Aurora B substrate phosphorylation.We reason that the PLK1-mediated priming phosphorylation is critical for orchestrating Aurora B activity in centromere which is essential for accurate chromosome segregation and faithful completion of cytokinesis.
基金supported by the National Natural Science Foundation of China(Grant Nos.39925018,30121001,30270293&90508002)the Chinese Academy of Sciences(Grant No.KSCX2-2-01)+3 种基金the Chinese 973 Project(Grant No.2002CB713700)the Chinese 863 Project(Grant No.2001AA215331)Chinese Minister of Education(Grant No.20020358051)American Cancer Society(Grant No.RPG-99-173-01).
文摘Kinesin superfamily of microtubule- based motor orchestrates a variety of cellular proc- esses. Recent availability of mammalian genomes has enabled analyses of kinesins on the whole ge- nome. Here we present a novel full-length kinesin prediction program (FKPP) for mammalian kinesin gene discovery based on a comparative genomics approach. Contrary to previous predictions of 94 kinesins, we identify a total of 134 potentially kinesin genes from mammalian genomes, including 45 from mouse, 45 from rat and 44 from human. In addition, FKPP synthesizes 25 potentially full-length mam- malian kinesins based on the partial sequences in the database. Surprisingly, FKPP reveals that full-length human CENP-E contains 2701 aa rather than 2663 aa in the database. Experimentation using sequence specific antibody and cDNA sequencing of human CENP-E validates the accuracy of FKPP. Given the remarkable computing efficiency and accuracy of FKPP, we reclassify the mammalian kinesin super- family. Since current databases contain many in- complete sequences, FKPP may provide a novel approach for molecular delineation of kinesins and other protein families.
基金supported by grants from the National Natural Science Foundation of China (81070363,30900497,31271518,31471275,31301121,31471268,31501095,and 31320103904)National Institutes of Health (CA164133,DK56292)+1 种基金Anhui Provincial Natural Science Foundation (1508085SMC213)China Postdoctoral Science Foundation (2014M560517).
文摘Endoplasmic reticulum(ER)stress is involved in ischemic preconditioning that protects various organs from ischemia/reperfusion(I/R)injury.We established an in vivo ER stress preconditioning model in which tunicamycin was injected into rats before hepatic I/R.The hepatic I/R injury,demonstrated by serum aminotransferase level and the ultra-structure of the liver,was alleviated by administration of tunicamycin,which induced ER stress in rat liver by activating inositol-requiring enzyme1(IRE1)andupregulating78 kDaglucose-regulated protein(GRP78).The proteomic identification for IRE1 binders revealed interaction and cooperation among receptor for activated C kinase 1(RACK1),phosphorylated AMPK,and IRE1 under ER stress conditions in a spatiotemporal manner.Furthermore,in vitro ER stress preconditioningwas induced by thapsigargin and tunicamycin in L02 and Hep G2 cells.Surprisingly,BCL2 was found to bephosphorylated by IRE1 under ER stress conditions to prevent apoptotic process by activation of autophagy.In conclusion,ER stress preconditioning protects against hepatic I/R injury,which is orchestrated by IRE1-RACK1 axis through the activation of BCL2.Our findings provide novel insights into the molecular pathways underlying ER stress preconditioning-elicited cytoprotective effect against hepatic I/R injury.
基金supported by the National Natural Science Foundation of China(31501130,31501095)China Postdoctoral Science Foundation(2014M560517)Anhui Provincial Natural Science Foundation(1508085SMC213)
