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Iai M Cheesema - One of the best experts on this subject based on the ideXlab platform.

  • quiescent cells Actively replenish cenp A nucleosomes to mAintAin Centromere identity And proliferAtive potentiAl
    Developmental Cell, 2019
    Co-Authors: Zachary S Swartz, Liliana S Mckay, Leah Ury, Abbas Padeganeh, Paul S Maddo, Kristi A Knouse, Iai M Cheesema
    Abstract:

    SummAry Centromeres provide A robust model for epigenetic inheritAnce As they Are specified by sequence-independent mechAnisms involving the histone H3-vAriAnt Centromere Protein A (CENP-A). PrevAiling models indicAte thAt the high intrinsic stAbility of CENP-A nucleosomes mAintAins Centromere identity indefinitely. Here, we demonstrAte thAt CENP-A is not stAble At Centromeres but is insteAd grAduAlly And continuously incorporAted in quiescent cells including G0-Arrested tissue culture cells And prophAse I-Arrested oocytes. Quiescent CENP-A incorporAtion involves the cAnonicAl CENP-A deposition mAchinery but displAys distinct requirements from cell cycle-dependent deposition. We demonstrAte thAt Plk1 is required specificAlly for G1 CENP-A deposition, whereAs trAnscription promotes CENP-A incorporAtion in quiescent oocytes. Preventing CENP-A deposition during quiescence results in significAntly reduced CENP-A levels And perturbs chromosome segregAtion following the resumption of cell division. In contrAst to quiescent cells, terminAlly differentiAted cells fAil to mAintAin CENP-A levels. Our work reveAls thAt quiescent cells Actively mAintAin Centromere identity providing An indicAtor of proliferAtive potentiAl.

  • the moleculAr bAsis for Centromere identity And function
    Nature Reviews Molecular Cell Biology, 2016
    Co-Authors: Kara L Mckinley, Iai M Cheesema
    Abstract:

    The Centromere is the region of the chromosome thAt directs its segregAtion in mitosis And meiosis. Although the functionAl importAnce of the Centromere hAs been AppreciAted for more thAn 130 yeArs, elucidAting the moleculAr feAtures And properties thAt enAble Centromeres to orchestrAte chromosome segregAtion is An ongoing chAllenge. Most eukAryotic Centromeres Are defined epigeneticAlly And require the presence of nucleosomes contAining the histone H3 vAriAnt Centromere Protein A (CENP-A; Also known As CENH3). Ongoing work is providing importAnt moleculAr insights into the centrAl requirements for Centromere identity And propAgAtion, And the mechAnisms by which Centromeres recruit kinetochores to connect to spindle microtubules.

Hansjurgen Thiesen - One of the best experts on this subject based on the ideXlab platform.

  • computAtionAl AnAlysis of high density peptide microArrAy dAtA with ApplicAtion from systemic sclerosis to multiple sclerosis
    Autoimmunity Reviews, 2012
    Co-Authors: Michael Hecker, Peter Lorenz, Felix Steinbeck, Li Hong, Gabriela Riemekasten, Uwe K Zettl, Hansjurgen Thiesen
    Abstract:

    Auto-Antibodies Are implicAted in the pAthophysiology of vArious Autoimmune diseAses. High-density peptide microArrAys incubAted with humAn serum cAn detect Antibody reActivities AgAinst thousAnds of peptides. This enAbles the identificAtion of new Auto-Antigens And the determinAtion of the pArts of Protein Antigens (epitopes) thAt Are recognized by Antibody pArAtopes. We discuss the utility of peptide microArrAys to investigAte epitope-Antibody-recognitions (EAR) from systemic sclerosis to multiple sclerosis. The technology cAn help to estAblish reliAble diAgnostic And prognostic biomArkers employing A combinAtion of Antigenic peptides. We describe the specifics of peptide microArrAy dAtA And present bioinformAtic methods for their AnAlysis. QuAlity control, dAtA pre-processing And the filtering of specific peptides Are demonstrAted on An exAmple dAtA set. Peptide microArrAys representing 24 selected Proteins by 3235 overlApping 15mer peptides were used to meAsure Antibodies in serum of 10 pAtients with limited cutAneous systemic sclerosis (SSC) And 10 heAlthy blood donors. The dAtA showed A spArse And skewed distribution, And we observed strong individuAl differences since mAny peptide sequences were bound by Antibodies of only one serum sAmple. In the serA of the SSc pAtients, but not of the heAlthy controls, we found Antibodies to three peptides MGPRRRSRKPEAPRR, TPTPGPSRRGPSLGA And GPSRRGPSLGASSHQ thAt shAre A similAr sequence motif (GP-R/S-RR). These peptides mAp to two known lineAr epitopes At the N-terminus of Centromere Protein A (CENPA), demonstrAting the utility of peptide microArrAys. Presented experimentAl And bioinformAtic ApproAch cAn be Applied in the sAme mAnner for multiple sclerosis reseArch.

Li Hong - One of the best experts on this subject based on the ideXlab platform.

  • computAtionAl AnAlysis of high density peptide microArrAy dAtA with ApplicAtion from systemic sclerosis to multiple sclerosis
    Autoimmunity Reviews, 2012
    Co-Authors: Michael Hecker, Peter Lorenz, Felix Steinbeck, Li Hong, Gabriela Riemekasten, Uwe K Zettl, Hansjurgen Thiesen
    Abstract:

    Auto-Antibodies Are implicAted in the pAthophysiology of vArious Autoimmune diseAses. High-density peptide microArrAys incubAted with humAn serum cAn detect Antibody reActivities AgAinst thousAnds of peptides. This enAbles the identificAtion of new Auto-Antigens And the determinAtion of the pArts of Protein Antigens (epitopes) thAt Are recognized by Antibody pArAtopes. We discuss the utility of peptide microArrAys to investigAte epitope-Antibody-recognitions (EAR) from systemic sclerosis to multiple sclerosis. The technology cAn help to estAblish reliAble diAgnostic And prognostic biomArkers employing A combinAtion of Antigenic peptides. We describe the specifics of peptide microArrAy dAtA And present bioinformAtic methods for their AnAlysis. QuAlity control, dAtA pre-processing And the filtering of specific peptides Are demonstrAted on An exAmple dAtA set. Peptide microArrAys representing 24 selected Proteins by 3235 overlApping 15mer peptides were used to meAsure Antibodies in serum of 10 pAtients with limited cutAneous systemic sclerosis (SSC) And 10 heAlthy blood donors. The dAtA showed A spArse And skewed distribution, And we observed strong individuAl differences since mAny peptide sequences were bound by Antibodies of only one serum sAmple. In the serA of the SSc pAtients, but not of the heAlthy controls, we found Antibodies to three peptides MGPRRRSRKPEAPRR, TPTPGPSRRGPSLGA And GPSRRGPSLGASSHQ thAt shAre A similAr sequence motif (GP-R/S-RR). These peptides mAp to two known lineAr epitopes At the N-terminus of Centromere Protein A (CENPA), demonstrAting the utility of peptide microArrAys. Presented experimentAl And bioinformAtic ApproAch cAn be Applied in the sAme mAnner for multiple sclerosis reseArch.

Minghua Zhu - One of the best experts on this subject based on the ideXlab platform.

  • expression And prognostic relevAnce of Centromere Protein A in primAry osteosArcomA
    Pathology Research and Practice, 2014
    Co-Authors: Xiaojun Feng, Minghua Zhu, Xue Huang, Shoumei Wang, Xinfeng Chen, Shuhui Zhang
    Abstract:

    Centromere Protein A (CENP-A) is one of the fundAmentAl components of the humAn Active kinetochore And plAys importAnt roles in cell-cycle regulAtion, cell survivAl, And genetic stAbility. The Aim of the present study wAs to explore the expression And prognostic significAnce of CENP-A in osteosArcomA. The results of reAl-time quAntitAtive PCR And Western blotting AnAlysis reveAled An enhAnced expression of CENP-A in osteosArcomAs relAtive to AdjAcent non-tumorous bone tissues At both mRNA And Protein levels. ImmunohistochemicAlly, 72 of the 123 osteosArcomA specimens (58.5%) hAd high expression of CENP-A. CENP-A overexpression wAs significAntly correlAted with tumor size (P=0.002), poor response to neoAdjuvAnt chemotherApy (P=0.016), locAl recurrence/lung metAstAsis (P=0.001), high Ki-67 index (P=0.004), And P53 positivity (P=0.005). MediAn overAll And recurrence-free survivAl time wAs significAntly shorter in pAtients with high-CENP-A osteosArcomAs thAn in those with low-CENP-A osteosArcomAs. MultivAriAte AnAlysis identified CENP-A As An independent poor prognostic fActor for osteosArcomA. In conclusion, our results demonstrAte thAt elevAted CENP-A expression is significAntly AssociAted with osteosArcomA progression And hAs An independent prognostic vAlue in predicting overAll And recurrence-free survivAl for pAtients with osteosArcomA.

  • shrnA tArgeted Centromere Protein A inhibits hepAtocellulAr cArcinomA growth
    PLOS ONE, 2011
    Co-Authors: Zhi Zhu, Shuhui Zhang, Lina Liu, Xiaozhe Cao, Li Wang, Hengjun Gao, Minghua Zhu
    Abstract:

    BAckground Centromere Protein A (CENP-A) plAys importAnt roles in cell-cycle regulAtion And genetic stAbility. Herein, we Aimed to investigAte its expression pAttern, clinicAl significAnce, And biologicAl function in hepAtocellulAr cArcinomA (HCC).

  • effect of sirnA tArgeting Centromere Protein A gene on biologicAl behAvior of hepg2 cells
    Chinese Journal of Pathology, 2008
    Co-Authors: Zhi Zhu, Ying Chen, Zhigang Luo, Min Shi, Minghua Zhu
    Abstract:

    Objective To study the influence of siRNA inhibition of CENP-A expression on the biologicAl behAvior of HepG2 cells.Methods Three pAirs of 21 bp reverse repeAted motifs of CENP-A tArget sequence with 9 spAcer were synthesized And inserted into vector pSilencerTM 2.1-U6 neo to generAte siRNA eukAryotic expression plAsmids.After stAble trAnsfection into HepG2 cells,cell growth,Apoptosis,cell cycles And plAte clone forming efficiency were investigAted.Expressions of CENP-A mRNA wAs monitored by the reverse trAnscriptAse polymerAse chAin reAction(RT-PCR).The Protein expression of CENP-A,bcl-2,BAx,p53,p21wAf1 And mdm2 were detected by Western-blotting.Results Two eukAryotic expression plAsmids with significAnt siRNA specific inhibition to the CENP-A gene were creAted.CompAred with control cells,HepG2 cells trAnsfected with the constructs showed G1 phAse delAy(P＜0.01)And cell number decreAse in the S phAse(P＜0.001),Along with An increAsed Apoptotic rAte(P=0.003).significAnt increAse of BAx expression And decreAsed bcl-2 expression(P≤0.001).The Protein expressions of p21wAf1 wAs higher And mdm2 wAs lower thAn those of the control groups.However,the wild type p53 Protein expression wAs not effected by CENP-A siRNA.Conclusions An Altered expression of CENP-A mAy be relAted to the proliferAtion of hepAtocellulAr cArcinomA through cell cycle regulAtion involving An Altered bel-2BAx expression,thAt mAy be p53 independent. Key words: Liver neoplAsms;  RNA,smAll interfering;  Apoptosis;  Gene expression regulAtion

  • expression of Centromere Protein A in hepAtocellulAr cArcinomA
    Chinese Journal of Pathology, 2007
    Co-Authors: Xiaohong Liu, Xiaozhe Cao, Li Wang, Minghua Zhu
    Abstract:

    OBJECTIVE To study the expression of Centromere Protein A (CENP-A) And its significAnce in hepAtocellulAr cArcinomA (HCC) And AdjAcent non-neoplAstic liver tissue. METHODS The expression levels of CENP-A mRNA in 20 sAmples of HCC And AdjAcent non-neoplAstic liver tissue were AnAlyzed by reverse trAnscription-polymerAse chAin reAction (RT-PCR) And reAl-time quAntitAtive polymerAse chAin reAction (qRT-PCR). ImmunohistochemicAl study for CENP-A And p53 Proteins wAs Also performed on tissue microArrAys contAining 80 sAmples of HCC And AdjAcent liver tissue. RESULTS The expression level of CENP-A mRNA in HCC (0.64 +/- 0.18) wAs higher thAn thAt in AdjAcent non-neoplAstic liver tissue (0.09 +/- 0.09) (t = 12.78, P < 0.01). Of the 80 sAmples of HCC, 57 cAses (71.25%) And 60 cAses (75%) expressed CENP-A And p53 Proteins respectively. The positivity rAtes of CENP-A And p53 Proteins in non-neoplAstic liver tissue were 43.75% (35/80) And 16.25% (13/80) respectively. There wAs A stAtisticAlly significAnt difference in CENP-A And p53 Protein expression between HCC And non-neoplAstic liver tissue (P < 0.01). The coincident rAte between CENP-A And p53 expression wAs 88.75% (71/80). Expression of CENP-A Protein showed A positive correlAtion with thAt of p53 Protein (r = 0.57, P < 0.01). CONCLUSION The over-expression of CENP-A occurs At trAnscriptionAl level And mAy be relAted to mAlignAnt proliferAtion of HCC viA possible interAction with p53 gene.

  • recent AdvAnces in biologic function of Centromere Protein A
    Chinese Journal of Pathology, 2006
    Co-Authors: Minghua Zhu
    Abstract:

    自从20世纪80年代着丝粒蛋白特异抗血清ACA被发现至今,现已有9种着丝粒蛋白被定名,其中着丝粒蛋白A(CENP-A)是最早被发现者之一. 近年来,关于CENP-A与肿瘤细胞增殖的关系越来越受到关注,本文就其生物学功能的研究进展做一综述。

Kenji Sugimoto - One of the best experts on this subject based on the ideXlab platform.

  • Centromere kinetochore locAlizAtion of humAn Centromere Protein A cenp A exogenously expressed As A fusion to green fluorescent Protein
    Cell Structure and Function, 2000
    Co-Authors: Kenji Sugimoto, Rika Fukuda, Michio Himeno
    Abstract:

    Three humAn Centromere Proteins, CENP-A, CENP-B And CENP-C, Are A set of AutoAntigens specificAlly recognized by AntiCentromere Antibodies often produced by pAtients with sclerodermA. Microscopic observAtion hAs indicAted thAt CENP-A And CENP-C locAlize to the inner plAte of metAphAse kinetochore, while CENP-B locAlizes to the Centromere heterochromAtin beneAth the kinetochore. The Antigenic structure, cAlled "prekinetochore", is Also present in interphAse nuclei, but little is known About its moleculAr orgAnizAtion And the relAtive position of these Antigens. Here, to visuAlize prekinetochore in living cells, we first obtAined A stAble humAn cell line, MDA-AF8-A2, in which humAn CENP-A is exogenously expressed As A fusion to A green fluorescent Protein of AequoreA victoriA. SimultAneous stAining with Anti-CENP-B And Anti-CENP-C Antibodies showed thAt the recombinAnt CENP-A colocAlized with the endogenous CENP-C And constituted smAll discrete dots AttAching to lArger Amorphous mAss of CENP-B heterochromAtin. When the cell growth wAs Arrested in G1/S phAse with hydroxyureA, CENP-B heterochromAtin wAs sometimes highly extended, while the relAtive locAtion between GFP-fused CENP-A And the endogenous CENP-C wAs not Affected. These results indicAted thAt the fluorescent CENP-A fAithfully locAlizes to the Centromere/kinetochore throughout the cell cycle. We then obtAined severAl mAmmAliAn cell lines where the sAme GFP-fused humAn CENP-A construct wAs stAbly expressed And their Centromere/kinetochore is fluorescent throughout the cell cycle. These cell lines will further be used for visuAlizing the prekinetochore locus in interphAse nuclei As well As AnAlyzing kinetochore dynAmics in the living cells.

  • Autoepitopes on AutoAntigen Centromere Protein A cenp A Are restricted to the n terminAl region which hAs no homology with histone h3
    Clinical and Experimental Immunology, 2000
    Co-Authors: Yoshinao Muro, N Azuma, Hiroki Onouchi, Mitoshi Kunimatsu, Yasushi Tomita, M Sasaki, Kenji Sugimoto
    Abstract:

    Anti-Centromere AutoAntibodies (ACA) Are commonly found in the serum of pAtients with A limited type of sclerodermA And other systemic Autoimmune diseAses. CENP-A is one of the mAjor Antigens AgAinst ACA And A histone H3-like Protein. To AnAlyse the AutoAntigenic epitopes of CENP-A, A series of truncAted peptides of humAn CENP-A were expressed in EscherichiA coli And immunoblotting AnAlysis wAs performed with 91 ACA+ serA. Eighty serA (88%) with the ACA reActed to the 52-Amino Acids N-terminAl region which is not homologous to H3, while no serA reActed to the C-terminus which hAs A sequence similArity with H3. Moreover, ELISA wAs Also employed in this study using two synthetic peptides corresponding to the Amino Acid sequences 3–17 (peptide A) And 25–38 (peptide B). Peptides A And B were reActive to 78 (86%) And 79 (87%) of ACA, respectively. Core Antigens of hepAtitis B virus (HBV) And hepAtitis C virus (HCV) hAve similAr sequences to peptide A And/or peptide B, but three serA contAining HBV without ACA And five serA contAining HCV without ACA were found to be reActive to neither peptide. Centromere locAlizAtion of CENP-A is dependent on the H3-like C-terminAl domAin which is not AutoAntigenic, while the Antigenic N-terminAl domAin, which might plAy unidentified functionAl roles, should be An importAnt region for the induction of ACA.