Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 分子醫學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42300
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor呂勝春(Sheng-Chung Lee)
dc.contributor.authorChiung-Wen Changen
dc.contributor.author張瓊文zh_TW
dc.date.accessioned2021-06-15T00:58:35Z-
dc.date.available2008-09-11
dc.date.copyright2008-09-11
dc.date.issued2008
dc.date.submitted2008-08-01
dc.identifier.citationAbrink M, Ortiz JA, Mark C, Sanchez C, Looman C, Hellman L, Chambon P, Losson R. Conserved interaction between distinct Krüppel-associated box domains and the transcriptional intermediary factor 1 beta. Proc Natl Acad Sci U S A. 2001 98:1422-1426
Aleem E, Kiyokawa H, Kaldis P. Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat Cell Biol 2005, 7:779-781
Ayyanathan K, Lechner MS, Bell P, Maul GG, Schultz DC, Yamada Y, Tanaka K, Torigoe K, Rauscher FJ 3rd. Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. Genes Dev. 2003,17:1855-1869
Barlev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, Berger SL. Acetylation of p53 activates transcription through recruitment of coactivators/
histone acetyltransferases. Mol. Cell 2001, 8:1243-1254
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A 2004, 101:12130-12135
Belhacène N, Maulon L, Guérin S, Ricci JE, Mari B, Colin Y, Cartron JP, Auberger P. Differential expression of the Kell blood group and CD10 antigens: two related membrane metallopeptidases during differentiation of K562 cells by phorbol ester and hemin. FASEB J 1998, 12:531-539
Brand C, Cipok M, Attali V, Bak A, Sampson SR. Protein kinase Cd participates in insulin-induced activation of PKB via PDK1. Biochem Biophys Res Commun 2006, 349:954-962
Brasher SV, Smith BO, Fogh RH, Nietlispach D, Thiru A, Nielsen PR, Broadhurst RW, Ball LJ, Murzina NV, Laue ED. The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J 2000, 19:1587-1597
Brown CE, Howe L, Sousa K, Alley SC, Carozza MJ, Tan S, Workman JL. Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit. Science, 2001, 292:2333-2337
Cammas F, Janoshazi A, Lerouge T, Losson R. Dynamic and selective interactions of the transcriptional corepressor TIF1 beta with the heterochromatin protein HP1 isotypes during cell differentiation. Differentiation. 2007, 75:627-637
Cammas F, Mark M, Dollé P, Dierich A, Chambon P, Losson R. Mice lacking the transcriptional corepressor TIF1beta are defective in early postimplantation development. Development 2000, 127:2955-2963
Chang CJ, Chen YL, Lee SC. Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression. Mol Cell Biol 1998, 18:5880-5887
Chen D, Dundr M, Wang C, Leung A, Lamond A, Misteli T, Huang S. Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins. J Cell Biol. 2005;168:41-54
Chen Q, Li H, De Lozanne A. Contractile ring-independent localization of DdINCENP, a protein important for spindle stability and cytokinesis. Mol Biol Cell. 2006;17:779-788
Clarke PR, Zhang C. Spatial and temporal coordination of mitosis by Ran GTPase. Nat Rev Mol Cell Biol. 2008, 9:464-477
Delcuve GP, He S, Davie JR. Mitotic partitioning of transcription factors. J Cell Biochem. 2008 May 5
Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM. Structure and ligand of a histone acetyltransferase bromodomain. Nature1999, 399:491-496
Dormann HL, Tseng BS, Allis CD, Funabiki H, Fischle W. Dynamic regulation of effector protein binding to histone modifications: the biology of HP1 switching. Cell Cycle. 2006, 5:2842-2851
E Minc, Y Allory, H J Worman, J C Courvalin, B Buendia. Localization and phosphorylation of HP1 proteins during the cell cycle in mammalian cells. Chromosoma. 1999 ;108:220-234
Eissenberg JC and Elgin SC. The HP1 protein family: getting a grip on chromatin. Curr Opin Genet Dev 2000, 10:204-210
Eissenberg JC. Decisive factors: a transcription activator can overcome heterochromatin silencing. Bioessays 2001, 23:767-771
Feinstein TN and Linstedt AD. Mitogen-activated protein kinase kinase 1-dependent Golgi unlinking occurs in G2 phase and promotes the G2/M cell cycle transition. Mol Biol Cell. 2007, 18:594-604
Fischle W, Tseng BS, Dormann HL, Ueberheide BM, Garcia BA, Shabanowitz J, Hunt DF, Funabiki H, Allis CD. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 2005, 438:1116-1122
Fischle W, Wang Y, Allis CD. Binary switches and modification cassettes in histone biology and beyond. Nature. 2003, 425:475-479
Gartsbein M, Alt A, Hashimoto K, Nakajima K, Kuroki T, Tennenbaum T. The role of protein kinase C delta activation and STAT3 Ser727 phosphorylation in insulin-induced keratinocyte proliferation. J Cell Sci 2006, 119:470-481
Goldman RD, Gruenbaum Y, Moir RD, Shumaker DK, Spann TP Nuclear lamins: building blocks of nuclear architecture. Genes Dev. 2002, 16:533-547
Gu W and Roeder RG. Activation of p53 sequence-specific DNA binding by
acetylation of the p53 C-terminal domain. Cell 1997:90, 595-606
Hackbarth JS, Galvez-Peralta M, Dai NT, Loegering DA, Peterson KL, Meng XW, Karnitz LM, Kaufmann SH. Mitotic phosphorylation stimulates DNA relaxation activity of human topoisomerase I. J Biol Chem. 2008, 283:16711-16722
Hallstrom, TC., and Nevins, JR. Specificity in the activation and control of transcription factor E2F-dependent apoptosis. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 10848-10853
Haynes SR, Dollard C, Winston F, Beck S, Trowsdale J, Dawid IB.
The bromodomain: a conserved sequence found in human, Drosophila and yeast
proteins. Nucleic Acids Res. 1992, 20:2603-2603
Henglein B, Chenivesse X, Wang J, Eick D, Bréchot C. Structure and cell cycle-regulated transcription of the human cyclin A gene. Proc Natl Acad Sci U S A 1994, 91:5490-5494
Hirota T, Lipp JJ, Toh BH, Peters JM. Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 2005, 438:1176-1180
Ito A, Lai CH, Zhao X, Saito S, Hamilton MH, Appella E, Yao TP. p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J. 2001, 20:1331–1340
Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, Yao TP. MDM2-HDAC1–mediated deacetylation of p53 is required for its degradation. EMBO J. 2002, 21:6236–6245
Jain N, Zhang T, Kee WH, Li W, Cao X. Protein kinase C delta associates with and phosphorylates Stat3 in an interleukin-6-dependent manner. J Biol Chem 1999, 274:24392-24400
Jeanmougin F, Wurtz JM, Le Douarin B, Chambon P, Losson R. The bromodomain revisited. Trends in Biochem. Sci. 1997, 22:151-153
Johansen KM, Johansen J. Regulation of chromatin structure by histone H3S10 phosphorylation. Chromosome Res. 2006, 14:393-404
Kaláb P, Pralle A, Isacoff EY, Heald R, Weis K. Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature. 2006, 440:697-701
Kellum, R. HP1 complexes and heterochromatin assembly. Curr. Top. Microbiol. Immunol. 2003, 274, 53-77
Kenrick M, Hancock S, Stubbs S, Thomas N. SiRNA screening of the cell cycle with two dynamic GFP sensors. Discovery Matters 2005, Issue 1:18-19. GE Healthcare, The Maynard Centre, Cardiff, UK.
Kitamura K, Mizuno K, Etoh A, Akita Y, Miyamoto A, Nakayama K, Ohno S. The second phase activation of protein kinase C delta at late G1 is required for DNA synthesis in serum-induced cell cycle progression. Genes Cells 2003, 8:311-324
Landsverk HB, Kirkhus M, Bollen M, Küntziger T, Collas P. PNUTS enhances in vitro chromosome decondensation in a PP1-dependent manner. Biochem J. 2005, 390:709-717
Letunic I, Goodstadt L, Dickens NJ, Doerks T, Schultz J, Mott R, Ciccarelli F, Copley RR, Ponting CP, Bork P. Recent improvements to the SMART domain-based sequence
annotation resource. Nucleic Acids Res. 2002, 30:242-244
Li M, Luo J, Brooks CL, Gu W. Acetylation of p53 inhibits its ubiquitination
by Mdm2. J. Biol. Chem. 2002, 277:50607–50611
Li X, Lee YK, Jeng JC, Yen Y, Schultz DC, Shih HM, Ann DK. Role for KAP1 serine 824 phosphorylation and sumoylation/desumoylation switch in regulating KAP1-mediated transcriptional repression. J Biol Chem. 2007, 282:36177-36189
Li X, Wong J, Tsai SY, Tsai MJ, O'Malley BW. Progesterone and glucocorticoid receptors recruit distinct coactivator complexes and promote distinct patterns of local chromatin modification. Mol Cell Biol 2003, 23:3763-3773
Li Y, Kao GD, Garcia BA, Shabanowitz J, Hunt DF, Qin J, Phelan C, Lazar MA. A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity. Genes Dev. 2006, 20:2566-2579
Liu L, Scolnick DM, Trievel RC, Zhang HB, Marmorstein R, Halazonetis, TD Berger, SL. p53 sites acetylated in vitro by P/CAF and p300 are acetylated in vivo in response to DNA damage. Mol. Cell Biol. 1999, 19:1202-1209
Loh YH, Zhang W, Chen X, George J, Ng HH Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 2007, 21:2545-2557
Manak JR, Wen H, Van T, Andrejka L, Lipsick JS. Loss of Drosophila Myb interrupts the progression of chromosome condensation. Nat Cell Biol. 2007, 9:581-587
Mascle XH, Germain-Desprez D, Huynh P, Estephan P, Aubry M. Sumoylation of the transcriptional intermediary factor 1beta (TIF1beta), the Co-repressor of the KRAB Multifinger proteins, is required for its transcriptional activity and is modulated by the KRAB domain. J Biol Chem. 2007, 282:10190-10202
Mao ML. Novel mechanisms for PKC family enzymes to regulate PI3K signaling pathway. ETD collection for Houston Academy of Medicine-Texas Medical Center. Paper AAI3046063. http://digitalcommons.library.tmc.edu/dissertations/AAI3046063
Mozziconacci J, Lavelle C, Barbi M, Lesne A, Victor JM. A physical model for the condensation and decondensation of eukaryotic chromosomes. FEBS Lett. 2006, 580:368-372
Mujtaba S, He Y, Zeng L, Yan S, Plotnikova O, Sachchidanand , Sanchez R, Zeleznik-Le NJ, Ronai Z, Zhou MM. Structural mechanism of the bromodomain of the coactivator
CBP in p53 transcriptional activation. Mol. Cell, 2004, 13:251-263
Nakajima H, Yonemura S, Murata M, Nakamura N, Piwnica-Worms H, Nishida E. Myt1 protein kinase is essential for Golgi and ER assembly during mitotic exit. J Cell Biol. 2008, 181:89-103
Nakatake M, Kakiuchi Y, Sasaki N, Murakami-Murofushi K, Yamada O. STAT3 and PKC differentially regulate telomerase activity during megakaryocytic differentiation of K562 cells. Cell cycle 2007, 6:1496-1501
Nasmyth K . Segregating sister genomes: the molecular biology of chromosome separation. Science 2002, 297:559-565
Nielsen AL, Ortiz JA, You J, Oulad-Abdelghani M, Khechumian R, Gansmuller A, Chambon P, Losson R. Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family. EMBO J 1999, 18:6385-6395
Nielsen AL, Sanchez C, Ichinose H, Cerviño M, Lerouge T, Chambon P, Losson R. Selective interaction between the chromatin-remodeling factor BRG1 and the heterochromatin-associated protein HP1alpha: EMBO J 2002, 21:5797-5806
Niiya F, Xie X, Lee KS, Inoue H, Miki T. Inhibition of cyclin-dependent kinase 1 induces cytokinesis without chromosome segregation in an ECT2 and MgcRacGAP-dependent manner. J Biol Chem. 2005, 280:36502-36509
Nishiyama A, Mochizuki K, Mueller F, Karpova T, McNally JG, Ozato K. Intracellular delivery of acetyl-histone peptides inhibits native bromodomain-chromatin interactions and impairs mitotic progression. FEBS Lett 2008, 582:1501-1507
Novotny-Diermayr V, Zhang T, Gu L, Cao X. Protein kinase C delta associates with the interleukin-6 receptor subunit glycoprotein (gp) 130 via Stat3 and enhances Stat3-gp130 interaction. J Biol Chem 2002, 277:49134-49142
Okada Y, Suzuki T, Sunden Y, Orba Y, Kose S, Imamoto N, Takahashi H, Tanaka S, Hall WW, Nagashima K, Sawa H. Dissociation of heterochromatin protein 1 from lamin B receptor induced by human polyomavirus agnoprotein: role in nuclear egress of viral particles. EMBO Rep. 2005, 6:452-457
Okamoto K, Kitabayashi I, Taya Y. KAP1 dictates p53 response induced by chemotherapeutic agents via Mdm2 interaction. Biochem Biophys Res Commun.2006, 351:216-222
Paulson JR. Inactivation of Cdk1/Cyclin B in metaphase-arrested mouse FT210 cells induces exit from mitosis without chromosome segregation or cytokinesis and allows passage through another cell cycle. Chromosoma. 2007, 116:215-225
Pawson T and Nash, P. Assembly of Cell regulatory systems through protein
interaction domains. Science 2003, 300:445-452
Peng H, Begg GE, Schultz DC, Friedman JR, Jensen DE, Speicher DW, Rauscher FJ 3rd Reconstitution of the KRAB-KAP1 repressor complex: a model system for defining the molecular anatomy of RING-B box-coiled-coil domain-mediated protein-protein interactions. J Mol Biol. 2000, 295:1139-1162
Potapova TA, Daum JR, Pittman BD, Hudson JR, Jones TN, Satinover DL, Stukenberg PT, Gorbsky GJ The reversibility of mitotic exit in vertebrate cells. Nature. 2006, 440:954-958
Preisinger C, Körner R, Wind M, Lehmann WD, Kopajtich R, Barr FA. Plk1 docking to GRASP65 phosphorylated by Cdk1 suggests a mechanism for Golgi checkpoint signalling. EMBO J. 2005, 24:753-765
Ramadan K, Bruderer R, Spiga FM, Popp O, Baur T, Gotta M, Meyer HH. Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin. Nature. 2007, 450:1258-1262
Rayman JB, Takahashi Y, Indjeian VB, Dannenberg JH, Catchpole S, Watson RJ, te Riele H, Dynlacht BD. E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex. Genes Dev 2002, 16:933-947
Reagan-Shaw S, Ahmad NSilencing of polo-like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: implications for the treatment of prostate cancer. FASEB J. 2005, 19:611-613
Rosson D and O'Brien TG. Constitutive c-myb expression in K562 cells inhibits induced erythroid differentiation but not tetradecanoyl phorbol acetate-induced megakaryocytic differentiation. Mol Cell Biol 1995, 15:772-779.
Ruan Q, Wang Q, Xie S, Fang Y, Darzynkiewicz Z, Guan K, Jhanwar-Uniyal M, Dai W Polo-like kinase 3 is Golgi localized and involved in regulating Golgi fragmentation during the cell cycle. Exp Cell Res. 2004, 294:51-59
Sabbattini P, Canzonetta C, Sjoberg M, Nikic S, Georgiou A, Kemball-Cook G, Auner
HW, Dillon N. A novel role for the Aurora B kinase in epigenetic marking of silent chromatin in differentiated postmitotic cells. EMBO J. 2007, 26:4657-4669
Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW, Appella E. DNA damage activates p53 through a phosphorylation–acetylation cascade. Genes. Dev. 1998, 12:2831-2841.
Schlessinger J and LemmonMA. SH2 and PTB domains in tyrosine kinase
signaling. Sci. STKE 2003, RE12
Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ 3rd. SETDB1: a novel KAP1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev 2002, 16:919-932
Schultz, D. C., Friedman, J. R., and Rauscher, F. J., III Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP1 form a cooperative unit that recruits a novel isoform of the Mi-2α subunit of NuRD. Genes Dev. 2001, 15:428–443.
Schultz J, Milpetz F, Bork P, Ponting CP. SMART, a simple modular architecture research tool: identification of signaling domains. Proc.Natl. Acad. Sci. USA 1998, 95:5857-5864.
Segil N, Guermah M, Hoffmann A, Roeder RG, Heintz N. Mitotic regulation of TFIID: inhibition of activator-dependent transcription and changes in subcellular localization. Genes Dev. 1996, 10:2389-2400
Shen S, Alt A, Wertheimer E, Gartsbein M, Kuroki T, Ohba M, Braiman L, Sampson SR, Tennenbaum T. PKCdelta activation: a divergence point in the signaling of insulin and IGF-1-induced proliferation of skin keratinocytes. Diabetes 2001, 50:255-264.
Shu H, Chen S, Bi Q, Mumby M, Brekken DL. Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line. Mol Cell Proteomics 2004, 3:279-286.
Smallwood A, Estève PO, Pradhan S, Carey M. Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev. 2007, 21:1169-1178
Sripathy SP, Stevens J, Schultz DC. The KAP1 corepressor functions to coordinate the assembly of de novo HP1-demarcated microenvironments of heterochromatin required for KRAB zinc finger protein-mediated transcriptional repression. Mol Cell Biol. 2006, 26:8623-8638
Srivastava J, Procyk KJ, Iturrioz X, Parker PJ. Phosphorylation is required for PMA- and cell-cycle-induced degradation of protein kinase Cdelta. Biochem J. 2002, 368:349-355
Sterner DE, Grant PA, Roberts SM, Duggan LJ, Belotserkovskaya R, Pacella LA, Winston F, Workman JL, Berger SL. Functional organization of the yeast SAGA complex: distinct components involved in structural integrity, nucleosome acetylation, and TATA-binding protein interaction. Mol. Cell Biol. 1999, 19:86-98.

Strahl BD, Allis CD. The language of covalent histone modifications. Nature 2000, 403:41-45
Sullivan BA, Karpen GH. Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol. 2004, 11:1076-1083
Sullivan M, Morgan DO. Finishing mitosis, one step at a time. Nat Rev Mol Cell Biol. 2007, 8:894-903
Sütterlin C, Hsu P, Mallabiabarrena A, Malhotra V Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells. Cell. 2002, 109:359-369
Sütterlin C, Polishchuk R, Pecot M, Malhotra V The Golgi-associated protein GRASP65 regulates spindle dynamics and is essential for cell division Mol Biol Cell. 2005, 16:3211-3222
Tamada H, Van Thuan N, Reed P, Nelson D, Katoku-Kikyo N, Wudel J, Wakayama T, Kikyo N. Chromatin decondensation and nuclear reprogramming by nucleoplasmin. Mol Cell Biol. 2006, 26:1259-1271
Tamkun JW, Deuring R, Scott MP, Kissinger M, Pattatucci AM, Kaufman TC, Kennison JA. Brahma: a regulator of Drosophila homeotic genes structurally related
to the yeast transcriptional activator SNF2/SWI2. Cell 1992, 68:561-572.
Tang D, Mar K, Warren G, Wang Y. Molecular mechanism of mitotic Golgi disassembly and reassembly revealed by a defined reconstitution assay. J Biol Chem. 2008, 283:6085-6094
Tanudji M, Shoemaker J, L'Italien L, Russell L, Chin G, Schebye XMGene silencing of CENP-E by small interfering RNA in HeLa cells leads to missegregation of chromosomes after a mitotic delay. Mol Biol Cell. 2004, 15:3771-3781
Thakar R, Csink AK , Changing chromatin dynamics and nuclear organization during differentiation in Drosophila larval tissue. J Cell Sci. 2005, 118:951-960
Thiru A, Nietlispach D, Mott HR, Okuwaki M, Lyon D, Nielsen PR, Hirshberg M, Verreault A, Murzina NV, Laue ED. Structural basis of HP1/PXVXL motif peptide interactions and HP1 localisation to heterochromatin. EMBO J 2004, 23:489-499
Tsay YG, Wang YH, Chiu CM, Shen BJ, Lee SC. A strategy for identification and quantitation of phosphopeptides by liquid chromatography/tandem mass spectrometry. Anal Biochem. 2000, 287:55-64
Vassallo MF and Tanese N. Isoform-specific interaction of HP1 with human TAFII130. Proc Natl Acad Sci U S A 2002, 99:5919-5924
Vigo E, Müller H, Prosperini E, Hateboer G, Cartwright P, Moroni MC, Helin K. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase. Mol Cell Biol 1999, 19:6379-6395
Viveiros MM, O'Brien M, Wigglesworth K, Eppig JJ. Characterization of protein kinase C delta in mouse oocytes throughout meiotic maturation and following egg activation. Biol Reprod 2003, 69:1494-1499
Wang C, Ivanov A, Chen L, Fredericks WJ, Seto E, Rauscher FJ 3rd, Chen J. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. EMBO J. 2005, 24:3279-3290
Wang C, Rauscher FJ 3rd, Cress WD, Chen J. Regulation of E2F1 function by the nuclear corepressor KAP1. J Biol Chem 2007, 282:29902-29909
Wang G, Ma A, Chow CM, Horsley D, Brown NR, Cowell IG, Singh PB. Conservation of heterochromatin protein 1 function. Mol Cell Biol 2000, 20:6970-6983
Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH. A protein interaction network for pluripotency of embryonic stem cells. Nature 2006, 444:364-368
Wang Y, Satoh A, Warren G. Mapping the functional domains of the Golgi stacking factor GRASP65. J Biol Chem. 2005, 280:4921-4928
Wang YH, Tsay YG, Tan BC, Lo WY, Lee SC. Identification and characterization of a novel p300-mediated p53 acetylation site, lysine 305. J Biol Chem. 2003, 278:25568-25576
White DE, Negorev D, Peng H, Ivanov AV, Maul GG, Rauscher FJ 3rd. KAP1, a novel substrate for PIKK family members, colocalizes with numerous damage response factors at DNA lesions. Cancer Res 2006, 66:11594-11599
Winston F and Allis CD. The bromodomain: a chromatin-targeting module? Nat. Struct. Biol. 1999, 6:601-604
Wolf D and Goff SP. TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells. Cell 2007, 131:46-57
Wolf F, Sigl R, Geley S. 'The end of the beginning': cdk1 thresholds and exit from mitosis. Cell Cycle. 2007, 6:1408-1411
Yan KS, Kuti M, Mujtaba S, Farooq A, Goldfarb MP, Zhou MM. SNT PTB domain conformation regulates interactions with divergent neurotrophic receptors. J. Biol. Chem. 2002, 277:17088-17094
Yang B, O'Herrin SM, Wu J, Reagan-Shaw S, Ma Y, Bhat KM, Gravekamp C, Setaluri V, Peters N, Hoffmann FM, Peng H, Ivanov AV, Simpson AJ, Longley BJ. MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res. 2007, 67:9954-9962
Yang F, Camp DG 2nd, Gritsenko MA, Luo Q, Kelly RT, Clauss TR, Brinkley WR, Smith RD, Stenoien DL. Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus. J Cell Sci. 2007, 120:4060-4070
Yang Z, Guo J, Chen Q, Ding C, Du J, Zhu X. Silencing mitosin induces misaligned chromosomes, premature chromosome decondensation before anaphase onset, and mitotic cell death. Mol Cell Biol. 2005, 25:4062-4074
Zeng L, Yap KL, Ivanov AV, Wang X, Mujtaba S, Plotnikova O, Rauscher FJ 3rd, Zhou MM. Structural insights into human KAP1 PHD finger-bromodomain and its role in gene silencing. Nat Struct Mol Biol. 2008, 15:626-33
Zhang W, Deng H, Bao X, Lerach S, Girton J, Johansen J, Johansen KM The JIL-1 histone H3S10 kinase regulates dimethyl H3K9 modifications and heterochromatic spreading in Drosophila. Development 2006, 133:229-235
Zharskaya OO, Barsukova AS, Zatsepina OV. Effect of roscovitine, a selective cyclin B-dependent kinase 1 inhibitor, on assembly of the nucleolus in mitosis. Biochemistry (Mosc) 2008, 73:411-419
Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, Schultz DC, Lukas J, Bekker-Jensen S, Bartek J, Shiloh Y. Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP1 dependent pathway. Nat Cell Biol. 2006, 8:870-876
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42300-
dc.description.abstract輔助轉錄調控因子TIF1beta(TIF1beta)/KAP1/TRIM28)是一個上位調控子,其功能與重要的角色為與heterochromtin protien 1 (HP1) 蛋白及其他染色質調控蛋白結合後,在某些特定的區域裡,調控染色質結構重組,使其鬆散或緻密,進而調控基因表現。其中TIF1beta 與HP1之間的交互作用,是經由位於TIF1beta序列上的HP1-box特性決定。這個具功能性的交互作用,對於生物在組織生長分化、個體發育、病毒抵抗,以及生理調控時的各項染色質的動態行為(動態特性)、穩定性的維持,乃至於基因表現的調控上,是很重要的。然而,闡述此等交互作用機制的文獻卻非常有限。TIF1beta目前被普遍認為是一個可經由多種'後轉譯修飾'的蛋白,修飾種類包括磷酸化、sumo化等。這些多種不同的修飾調控在不同的基因事件裡,皆扮演重要的角色。
本文的第一部分論述:經由PKC訊息調控途徑致使S473位置磷酸化後的TIF1beta,具有使G1-S細胞週期特異性基因活化的功能 。
TIF1beta/phorpho-Ser473 修飾在細胞周期的S-Phase與M-Phase中,被磷酸化的量顯著的提高,是一個受細胞周期調控的修飾位置。經由免疫化學反應及染色質免疫化學沉澱法分析發現,TIF1beta/Ser473 的磷酸化導致細胞週期調控的特異性基因cyclin A,cdc2,與cdc25A的活化。此誘導活化的發生,係由於TIF1beta與HP1的作用能力受到TIF1beta自身的S473被磷酸化所抑制。無法致磷酸話的TIF1beta/S473A與HP1beta共同存在於G1時期的細胞核間質裡,大量表現TIF1beta/S473A造成細胞停留在G2/M細胞週期的比例增加。TIF1beta/Ser473在細胞週期S phase 中的磷酸化,是經由PKCdelta訊息傳導途徑所媒介。TIF1beta/S473磷酸化的程度,在循環分裂的增殖細胞裡,明顯的比分化的細胞高。顯示TIF1beta/S473 磷酸化與去磷酸化,在細胞生長調控上,扮演重要的角色。
論文的第二部分論及:TIF1beta在細胞有絲分裂期間,透過自身的動態高度磷酸化調控其與染色質/染色體的相對分佈,具有維持細胞正常分裂增生的重要角色。
在TIF1beta的表現被基因功能性剔除後的HeLa(具有較低的p53功能活性)細胞株中觀察到細胞因此而產生不正常的外形改變化與細胞凋亡。這些現象係由這些細胞無法完成正常的有絲分裂所導致而成。經由流式細胞儀,免疫化學染色,和即時動態活細胞攝影術分析有絲分裂,這些細胞會產生錯誤的分裂溝決定位置,有絲分裂延遲或無法進行,與呈現染色質分佈不均等的現象。最後,細胞走向凋亡的途徑。
TIF1beta僅在M-phase的窗型期時,呈現高度磷酸化的狀態。利用LC/MS/MS分析技術,已經有至少三個磷酸化位置被分離鑑定出來。他们分別是位置S752,S757,和S473。TIF1beta透過自身的高度磷酸化狀態被排擠在具有高度緻密結構的染色體外圍的細胞質空間裡。在有絲分裂期間,TIF1beta會逐漸降低它的磷酸化狀態。有絲分裂後期,去高磷酸化的TIF1beta才具有與重新構建的染色質組成份子重新結合的能力。說明了藉由本身磷酸化的調節,TIF1beta在有絲分裂過程中具有無可替代的功能。
zh_TW
dc.description.abstractThe transcriptional intermediary factor TIF1beta(TIF1beta)/KAP1/TRIM28) is an epigenetic regulator, functions in gene expression and chromatin remodeling at specific loci by association with members of the heterochromatin protein 1 (HP1) family and various other chromatin factors. The interaction between TIF1beta and HP1 depend on the HP1-box of TIF1beta. This functional interaction is crucial for chromatin dynamics, maintenance and gene regulation during differentiation, development, viral restriction, and cellular physiological regulation. However, the underlying mechanism of how the interaction is regulated remains poorly understood. TIF1beta is a multiply modificated proteins. The modifications include phosphorylation and sumoylation. These modifications play important role(s) in regulating its activity at different events.
In the thesis part one, these studies conclude that the PKCdelta pathway mediated phosphorylation on TIF1beta/S473 is important for activation of G1-S cell cycle gene. The Ser473 of TIF1beta locates near the HP1b-binding motif, PXVXL. Phosphorylation of TIF1beta at Ser473 is cell cycle regulated which is elevated during S phase and M-phase. The dynamical alteration of which is functionally associated with cell cycle genes expression. Phosphorylation of TIF1beta/Ser473 coincides with the induction of cyclin A, cdc2, and cdc25A, due to the interaction with HP1beta is compromised by TIF1beta/phospho-S473 itself. Non-phsophorylated form TIF1beta/S473A preferentially associated with HP1beta in G1-phase nuclear matrix and affect cell cycle progression with more cell population stall in G2/M-phase while it is over-expressed. The phosphorylation of TIF1beta/Ser473 in early S phase is mediated by the PKCdelta pathway and is closely related to cell proliferation.
In the thesis part two, these studies conclude that TIF1beta is functionally important for mitotic progression through its dynamically regulated hyperphosphorylation during mitosis. The abnormal cell morphology and apoptosis phenotype in TIF1beta knockdown HeLa cells is due to the failure to complete the mitotic phase. The failure in cleavage furrow determination, mitotic delay, gradually having unevenly distributed chromatin, and finally apoptosis, are revealed by FACs, immunostaining, and Time Lapse Cinematography. TIF1beta exhibits a hyperphosphorylation state only in M-phase. At least three phosphorylation sites, S757, S752, and S473 are identified by LC/MS/MS. The exclusion of TIF1beta from M-phase chromosome is due to its hyperphosphorylation. The re-orchestration of TIF1beta with reorganized chromatin is tightly correlated with its gradually decreased phosphorylation level during mitosis. The functional TIF1beta in M-phase may coincide with the mitotic failure observed in TIF1beta knockdown HeLa cells.
en
dc.description.provenanceMade available in DSpace on 2021-06-15T00:58:35Z (GMT). No. of bitstreams: 1
ntu-97-D89448001-1.pdf: 6599109 bytes, checksum: f3b0d833e7fe6cf6aea77cdf6a2dfe33 (MD5)
Previous issue date: 2008
en
dc.description.tableofcontentsSummary P7
中文摘要 P9
Abstract (Part I)
Phosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1beta/KAP1 P11
Abstract (Part II)
TIF1beta is functional important through its dynamically regulated hyperphosphorylation in mitotic progression P13
1. Introduction
Part I
Phosphorylation at Ser473 regulates heterochromatin
protein 1 binding and corepressor function of TIF1beta/KAP1
1.1 General functions of TIF1beta and HP1beta P15
1.2 Functions of TIF1beta with HP1beta in differentiation,
developement and viral restriction P17
1.3 Post-translational modifications on TIF1beta P20
1.3-1 Phosphorylation at S824 P20
1.3-2 Sumoylations P21
1.3-3 Phosphorylation at S473 P22
1.4 Cell cycle regulation P22
1.5 PKC family kinases P24
Part II
TIF1beta is functional important through its dynamically regulated hyperphosphorylation in mitotic progression
1.6 Apoptosis phenotype reported in TIF1beta knockdown
cells P26
1.7 Similar morphology due to mitotic failure P28
1.8 Chromatin structure and histone modifications in M-
phase P29
1.9 Mitosis onset and exit P31
1.10 Cytokinesis & Roscovitine P33
1.11 Molecular transport during Mitosis P35
1.12 Transcription-related factors during Mitosis P37
2. Materials and Methods
2.1 Antibodies P39
2.2 Plasmids P39
2.3 Chemicals P41
2.4 Cell cultures P41
2.5 Biochemical Analysis: cell lysate extraction,
Immunoprecipitation, recombinant proteins, in vitro
pull-down, and western blotting P42
2.6 CIP P43
2.7 In vitro transcription and translation P43
2.8 Chromatin immunoprecipitation assays P44
2.9 Immunostaining P46
2.10 Flow cytometry P47
2.11 RNA extraction and Real-time PCR P47
2.12 Nuclear matrix extraction P48
2.13 Time Lapse Cinematography P49
2.14 In gel digestion P49
Part I
Phosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1beta/KAP1
3. Results
3.1 Characterization of TIF1beta and phosphorylated
TIF1beta/Ser473 Antibodies (Fig. 1A-1C) P51
3.1-1 Characterzation of TIF1beta/S473 in M-phase (Fig. 1D)
P52
3.2 Phosphorylation of TIF1beta/Ser473 is dynamically
regulated during cell cycle progression (Fig. 2A-2D) P52
3.2-1 TIF1beta/S473A is preferentially colocalized with HP1
beta in nuclear matrix (Fig. 2E) P54
3.2-2 Supporting resultes from references
- The fluctuation and expression timing of cyclins
during cell cycle (Table. 2F) P55
- FACs analysis of cell cycle distribution for 0 –
44 hours of thymidine released HeLa cells (ref,
Figure 2G) P55
3.3 Phosphorylation of TIF1beta/Ser473 compromises
interaction between HP1beta and TIF1beta P55
3.4 TIF1beta regulates key genes expression during G1 to S-
phase cell cycle progression (Fig. 4A-4D, Table 4E) P57
3.5 Phosphorylation of TIF1beta/Ser473 in S phase is
mediated by PKC pathway (Fig. 5A-5H) P60
3.6 Level of phosphorylated TIF1beta/Ser473 is reduced in
megakaryocytic differentiated K562 cells (Fig. 6A) P61
3.6-1 The steady state level of TIF1beta/phospho-S473
in different mouse tissue (Fig. 6B) P62
4. Discussion P63
5. List of Figures and Tables (legends included)
5.1 Figure 1A 1B 1C (3.1) P67
5.1-1 Figure 1D (3.1-1) P68
5.2 Figure 2A 2B 2C 2D (3.2) P69
5.2-1 Figure 2E (3.2-1) P71
5.2-2 Figure 2F 2G (3.2-2) P72
5.3 Figure 3A 3B 3C 3D (3.3) P73
5.4 Figure 4A 4B 4C 4D Table 4E (3.4) P75
5.5 Figure 5A 5B 5C 5D 5E 5F 5G 5H (3.5) P77
5.6 Figure 6A (3.6) P79
5.6-1 Figure 6B (3.6-1) P80
Part II
TIF1beta is functional important through its dynamically regulated hyperphosphorylation in mitotic progression
3. Results
3.1 HeLa cell is morphologically abnormal when TIF1beta is
knockdown by siRNA (Fig. 1A-1D) P82
3.2 Abnormal cell morphology observed in interphase is due
to mitotic failure in TIF1beta knockdown cells (Fig. 2A- 2D) P82
3.2-1 Live cell images of mitotic HeLa progression by Time
Lapse Cinematography (Supplemental Videos 2E, 2F) P84
3.3 TIF1beta is dynamically regulated by phosphorylation
during mitosis (Fig. 3A-3C) P85
3.3-1 The predicted phosphorylation sites on TIF1beta
(Table 3D) P85
3.3-2 HP1 binding domain is relatively important for the
nuclear localization of TIF1beta (Fig. 3E) P86
3.3-3 S757 and S752 are responsible for the
hyperphosphorylation state of TIF1beta in
prometaphase (Fig. 3F, 3G) P86
3.4 The hypo-phosphorylated TIF1beta is important for its
reassociation with reorganized/decondensed chromatin in
the end of mitosis (Fig. 4A-4D) P87
3.4-1 TIF1beta is dispersed into mitotic cytoplasm with cdk1 (Fig. 4E) P90
3.5 TIF1beta may shuttle with Giantin or GRASp65 in mitotic
cytoplasm (Fig. 5A, 5B) P90
3.6 TIF1beta indirectly interacts with actinin 4 in M-phase
(Fig 6A, 6B) P90
4. Discussion P92
5. List of Figures and Tables (legends included)
5.1 Figure 1A 1B 1C 1D (3.1) P97
5.2 Figure 2A 2B 2C 2D (3.2) P98
5.2-1 Supplemental Videos 2E 2F (3.2-1) P100
5.3 Figure 3A 3B 3C (3.3) P101
5.3-1 Table 3D (3.3-1) P102
5.3-2 Figure 3E (3.3-2) P103
5.3-3 Figure 3F 3G (3.3-3) P104
5.4 Figure 4A (3.4) P105
5.4 Figure 4B 4C (3.4) P106
5.4 Figure 4D (3.4) P107
5.4-1 Figure 4E (3.4-1) P108
5.5 Figure 5A 5B (3.5) P109
5.6 Figure 6A 6B (3.6) P110
6. Reference P111
Appendix P122
dc.language.isoen
dc.subject組蛋白zh_TW
dc.subject細胞分化zh_TW
dc.subject細胞週期zh_TW
dc.subject磷酸化zh_TW
dc.subject有絲分裂zh_TW
dc.subject染色質/染色體zh_TW
dc.subjectcdk1en
dc.subjectTIF1beta/KAP1en
dc.subjectheterochromatin protein 1(HP1)en
dc.subjectphosphorylationen
dc.subjectcell cycleen
dc.subjectE2Fen
dc.subjectPKCen
dc.subjectdifferentiationen
dc.subjectmitosisen
dc.subjecthistone codeen
dc.subjectchromatinen
dc.title輔助抑制子TIF1β/KAP1於Ser473位置磷酸化後對其結合HP1蛋白能力和本身抑制功能之調控zh_TW
dc.titlePhosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1β/KAP1en
dc.typeThesis
dc.date.schoolyear96-2
dc.description.degree博士
dc.contributor.oralexamcommittee李芳仁(Fang-Jen Lee),張?仁(Ching-Jin Chang),阮麗蓉(Li-Jung Juan),陳宏文(Hung-Wen Chen)
dc.subject.keyword磷酸化,細胞週期,染色質/染色體,細胞分化,有絲分裂,組蛋白,zh_TW
dc.subject.keywordTIF1beta/KAP1,heterochromatin protein 1(HP1),phosphorylation,cell cycle,E2F,PKC,differentiation,mitosis,histone code,chromatin,cdk1,en
dc.relation.page122
dc.rights.note有償授權
dc.date.accepted2008-08-02
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept分子醫學研究所zh_TW
顯示於系所單位:分子醫學研究所

文件中的檔案:
檔案 大小格式 
ntu-97-1.pdf
  未授權公開取用
6.44 MBAdobe PDF
顯示文件簡單紀錄


系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved