(18.206.177.17) 您好!臺灣時間:2021/04/11 03:09
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:萬長鑫
研究生(外文):WAN, CHANG-XIN
論文名稱:Aurora-A磷酸化SLAN之分子機制與細胞功能分析
論文名稱(外文):Molecular Mechanisms and Cellular Function for the Aurora-A Induced SLAN Phosphorylation.
指導教授:余長澤
指導教授(外文):YU, CHANG-TZE
口試委員:吳俊錡邱紹智夏君毅
口試日期:2018-06-08
學位類別:碩士
校院名稱:國立暨南國際大學
系所名稱:應用化學系
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:中文
論文頁數:88
中文關鍵詞:Aurora-ASLAN14-3-3Cytokinesis
外文關鍵詞:Aurora-ASLAN14-3-3Cytokinesis
相關次數:
  • 被引用被引用:0
  • 點閱點閱:42
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
Aurora-A是一個致癌性serine/threonine蛋白質激酶,負責調控細胞分裂期的行進。文獻顯示高量或抑制Aurora-A表現能引發cytokinesis的失敗並產生多核細胞,且Aurora-A能磷酸化細胞分裂期中軸線多個未知因子,並控制其細胞內的分佈,顯示此磷酸化及可能是Aurora-A控制cytokinesis的關鍵。為了尋找參與在cytokinesis的Aurora-A下游受質,本論文鎖定一細胞分裂期調控因子SLAN。本實驗先前的研究顯示,SLAN為一具潛力的抑癌蛋白,高量表現時會引發細胞分裂期停滯,有些細胞甚至會跳過cytokinesis進入細胞間期而造成多核細胞。由於Aurora-A會磷酸化SLAN,因此我們便提出假說:Aurora-A是否透過磷酸化SLAN來調控cytokinesis。本論文透過分析以下幾項研究議題來測試以上假說,包括分析Aurora-A磷酸化SLAN的分子機制、確認磷酸化位點、分析此磷酸化對於細胞分裂期或cytokinesis的可能調控效應、以及其相應分子作用機制。本論文指出,Aurora-A磷酸化SLAN需要透過鷹架蛋白14-3-3來將前兩者聚集在一起,且磷酸化位點發生於T573,此磷酸化的SLAN能透過調整RhoA來控制cytokinesis的進行。總之,本論文的研究結果顯示,Aurora-A/SLAN/14-3-3為一新型的cytokinesis調控途徑。
Aurora-A is an oncogenic serine/threonine kinase upregulated in mitosis. Overexpression or silence of Aurora-A induces cytokinesis failure and thereby production of multiple nuclei, implying the engagement of Aurora-A in the control of cytokinesis. Aurora-A is documented phosphorylating cytoplasmic unidentified factors at spindle midzone, and responsible for the spindle midzone- or metaphase plate- targeting of these factors, indicating that Aurora-A likely controls cytokinesis via phosphorylating and in turn midzone localization of its downstream substrates. To search for these factors, we noticed SLAN, a potential tumor suppressor and mitotic regulator guiding mitosis progression and cytokinesis through unknown mechanisms. The previous study in our laboratory shows that SLAN interacts with Aurora-A, and Aurora-A phosphorylates SLAN in an in vitro kinase. Moreover, overexpression of SLAN induces the formation of multiple nuclei, these observations fueling us to speculate a plausible hypothesis where Aurora-A controls cytokinesis through phosphorylation of SLAN. Hence, the thesis focuses itself on testing this hypothesis by proposing several aims, including identifying the molecular mechanisms by which Aurora-A phosphorylates SLAN, mapping the Aurora-A-catalyzed phosphorylation sites on SLAN, determining the potential regulatory effects of SLAN phosphorylation on cytokinesis, and unraveling how Aurora-A/SLAN cascade regulates cytokinesis. The study based on a series of analyses shows that Aurora-A interacts with and phosphorylates SLAN via the help of the scaffold protein 14-3-3, and Aurora-A phosphorylates SLAN at T573, which greatly stimulates M phase arrest and the formation of multiple nuclei. Further mechanistic analyses reveal the involvement of RhoA as one of the key factors downstream to Aurora-A/SLAN axis during cytokinesis. Taken together, the study demonstrates Aurora-A/SLAN/14-3-3 as a novel regulatory axis controlling cytokinesis.
目次
摘要………………………………………………………………………………………i
Abstract...……………………………………………………………………………….iii
目次………………………………………………………………...……………………v
圖目次…………………………………………………………………..………………ix
第壹章 緒論…………………………………………...………………...….…………..1
第一節 癌症與Aurora kinase A (Aurora-A)………...…………....……………….1
第二節 SLAN………………………………………………...................................4
第三節 中軸線調節因子Centralspindlin………........……………...…..………6
第四節 14-3-3……..…………………….…………………………..………….8
第五節 研究動機目的與鎖定議題…...……………………………………………10
第貳章 實驗材料與方法…………………………………………………………..11
第一節 實驗材料………………………………………………...………………11
一、抗生素(Antibiotics)……………………………...……...………….…......11
二、勝任細胞(Competent Cells)………………….….……..………………….11
三、細胞株(Cell line)…………………….………….…………………...….…..11
四、細胞轉染試劑(Transfection reagent)………….…………...……………….11
五、抗體(Antibody)………………………………….…………………….......12
六、shRNA……………………………………………………………………….14
第二節 實驗試劑配製…………………………...…………………………………15
一、Luria-Bertain 細菌培養液(LBmedium)…………………..………………..15
二、DNA 瓊膠(agarose)配製…………............…………………………….......15
三、Luria-Bertain 細菌培養基(LB agar plate)………………....……….………16
四、DMEM細胞培養液………………………………………………….………16
五、勝任細胞配製溶液……………………………………….…….….………16
六、DMEM細胞凍存培養液…………….………………………..……………..17
七、胰蛋白酶-乙二胺四乙酸四鈉消化液(Trypsin-EDTA)………………….17
八、10倍Tris-borate-EDTA 緩衝溶液(10X TBE buffer)………..……..….……18
九、聚丙烯醯胺膠體電泳分離膠體(SDS-PAGE)………………………….….18
十、免疫螢光染色試劑-PLP 固定溶液…………………………….………...19
十一、免疫螢光染色試劑-細胞通透性/蛋白質阻斷溶液(Permeabilization/blocking solution)………………………………….…...19
十二、免疫螢光染色試劑-清洗溶液(Wash soluion)…………………..…….20
十三、10倍全濕式電泳轉漬緩衝溶液(Transfer buffer)…………………..20
十四、細胞溶解緩衝溶液(Cell lysis buffer)…………………..……………..21
十五、免疫沉澱法清洗溶液(IP wash buffer)……………...…………….…..21
十六、西方墨點法蛋白質阻斷溶液…...……………………………………..22
十七、4倍SDS電泳追蹤染劑………….……………………………………..22
十八、聚丙烯醯胺膠體電泳焦集膠體.………….……………………..…….23
十九、10倍磷酸鹽緩衝溶液…………...…….……………………………….24
二十、10倍蛋白質電泳緩衝溶液…………………………………………….24
二十一、10倍TBST緩衝溶液…………………………………………………..25
第三節 實驗方法………………………………………………………………25
一、質體製備…………………………………………………………………..25
二、細胞培養…………………………………………………………………..27
三、遞送外來核酸於人類細胞………………………………….……………….28
四、蛋白質分析…………………………………………...…………………….29
五、細胞增生分析……………………………………………………………32
第參章 實驗結果…………………………………………………………………..33
第一節 Aurora-A 對SLAN 磷酸化之位點分析……………………….……33
第二節 Aurora-A磷酸化SLAN狀態對於M phase的影響…….....................34
第三節 SLAN p573和SLAN np573在細胞內之分佈………..……......……34
第四節 MKLP1、CYK4和14-3-3ղ對於SLAN於M phase分佈之影響.......…34
第五節 14-3-3ղ調控SLAN p573含量……………….......…………………...35
第六節 14-3-3ղ透過連結Aurora-A與SLAN去產生SLAN p573..........……35
第七節 Aurora-A通過14-3-3ղ和SLAN來抑制cytokinesis………………....36
第八節 SLAN np573能連結並活化RhoA…………………………………....37
第九節 SLAN監控cytokinesis的進行………………………………………38
第十節 PP1α、PP2A對SLAN p573進行去磷酸化…………………………..38
第肆章 討論與未來研究方向……………………………………………………..39
第一節 Aurora-A磷酸化SLAN於 T573點位……….………..…..………..39
第二節 14-3-3η通過兜攏Aurora-A和SLAN的交互作用來調控pSLAN的產生……………………………………………………………….....39
第三節 Aurora-A通過14-3-3η促進SLAN磷酸化進而抑制cytokinesis.......................................................….....................….……40
第四節 SLAN p573與np573具有相反之細胞功能..........................................40
第五節 RhoA和npSLAN之間的交互調控…..……………………....……..41
第伍章 結論………………………………………………………………………..42
參考文獻……………………………………………………………………………….44

圖目次
附圖一、台灣衛生署公佈105年度國人十大死因,仍以惡性腫瘤為首……...……..3
附圖二、Aurora-A會磷酸化全長SLAN和SLAN474-1101而非2-455…………….5
附圖三、Centraspindline在胞質分裂過程中調節赤道皮層ECT2和RhoA的積累….7
附圖四、SLAN在cytokinesis的分子機制…………………..……………………...42
圖一、Aurora-A 磷酸化SLAN 於T573…..…………….………….............................66
圖二、Aurora-A磷酸化SLAN狀態對於M phase的影響…….……..…..……………67
圖三、SLAN p573在M phase細胞內之分佈…………………………….……….……69
圖四、MKLP1、CYK4和14-3-3ղ對於pSLAN於M phase分佈之影響.........................70
圖五、SLAN p573與中軸線調節因子是否有交互作用......................………….….....72
圖六、14-3-3ղ調控SLAN p573的表現量........................................….……………….74
圖七、14-3-3ղ透過兜攏Aurora-A與SLAN去產生p573...........……………………..75
圖八、Aurora-A通過14-3-3ղ和SLAN來抑制cytokinesis………………...………….78
圖九、RhoA和npSLAN在M phase後期有交互作用………………………..……….80
圖十、SLAN np573在M phase細胞內之分佈………….......…………………..……..82
圖十一、MKLP1、CYK4、ECT2、RhoA對於npSLAN在M phase分佈之影響………83
圖十二、SLAN磷酸化狀態調節RhoA活性……………………………...…………...84
圖十三、抑制SLAN表現加速M phase行進………………………………………….86
圖十四、PP1α、PP2A降低磷酸化SLAN的含量…………………………………….88

李殿強, 可能抑癌蛋白SLAN對於細胞週期調控之研究, 國立暨南國際大學應用化學系生醫碩士班, 2008

郭奕群, 探討PRMT5甲基化HURP的機轉及其在細胞中的生理意義, 國立暨南國際大學應用化學系生醫碩士班, 2015

顧家鳳, 由決定SLAN功能性區段和研究SLAN與Aurora-A之相互調控分析之分子活性, 國立暨南國際大學應用化學系生醫碩士班, 2010

陳可心, 探討SLAN在肺癌細胞中扮演的角色, 國立暨南國際大學應用化學系生醫碩士班, 2010

Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future. J Clin Oncol. 2005 May 10;23(14):3175-85.

Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell. 2003 Jan;3(1):51-62.

Andrews PD. Aurora kinases: shining lights on the therapeutic horizon? Oncogene. 2005 Jul 28;24(32):5005-1

Andrianantoandro E, Pollard TD. Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell. 2006 Oct 6;24(1):13-23.

Anna S. Nikonova, Igor Astsaturov, Ilya G. Serebriiskii, Roland L. Dunbrack, Jr., and Erica A. Golemis. Aurora-A kinase (AURKA) in normal and pathological cell growth. Cell Mol Life Sci. 2013 Feb; 70(4): 661–687.

Bai M, Ni J, Shen S, Huang Q, Wu J, Le Y, Yu L. Aurora-A kinase-inactive mutants disrupt the interaction with Ajuba and cause defects in mitotic spindle formation and G2/M phase arrest in HeLa cells. BMB Rep. 2014 Nov;47(11):631-6.

Bai M, Ni J, Wu J, Wang B, Shen S, Yu L. A novel mechanism for activation of Aurora-A kinase by Ajuba. Gene. 2014 Jun 10;543(1):133-9.

Barr AR, Gergely F. Aurora-A: the maker and breaker of spindle poles. J Cell Sci. 2007 Sep 1;120(Pt 17):2987-96.

Barretta ML, Spano D, D'Ambrosio C, Cervigni RI, Scaloni A, Corda D, Colanzi A. Aurora-A recruitment and centrosomal maturation are regulated by a Golgi-activated pool of Src during G2. Nat Commun. 2016 May 31;7:11727.

Bastos RN, Penate X, Bates M, Hammond D, Barr FA. CYK4 inhibits Rac1-dependent PAK1 and ARHGEF7 effector pathways during cytokinesis. J Cell Biol. 2012 Sep 3;198(5):865-80.

Basant A, Lekomtsev S, Tse YC, Zhang D, Longhini KM, Petronczki M, Glotzer M. Aurora B kinase promotes cytokinesis by inducing centralspindlin oligomers that associate with the plasma membrane. Dev Cell. 2015 Apr 20;33(2):204-15.

Berdnik D, Knoblich JA. Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis. Curr Biol. 2002 Apr 16;12(8):640-7.

Bignold LP, Coghlan BL, Jersmann HP. Cancer morphology, carcinogenesis and genetic instability: a background. EXS. 2006;(96):1-24.
Bischoff JR, Plowman GD. The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis. Trends Cell Biol. 1999 Nov;9(11):454-9.

Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, Schryver B, Flanagan P, Clairvoyant F, Ginther C, Chan CS, Novotny M, Slamon DJ, Plowman GD. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 1998 Jun 1;17(11):3052-65.

Breznau EB, Murt M, Blasius TL, Verhey KJ, Miller AL. The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis. J Cell Sci. 2017 May 15;130(10):1809-1821.

Buvelot S, Tatsutani SY, Vermaak D, Biggins S. The budding yeast Ipl1/Aurora protein kinase regulates mitotic spindledisassembly. J Cell Biol. 2003 Feb 3;160(3):329-39.

Caban K, Copeland PR. Size matters: a view of selenocysteine incorporation from the ribosome. Cell Mol Life Sci. 2006 Jan;63(1):73-81.

Cahill S, Smyth P, Finn SP, Denning K, Flavin R, O'Regan EM, Li J, Potratz A, Guenther SM, Henfrey R, O'Leary JJ, Sheils O. Effect of ret/PTC 1 rearrangement on transcription and post-transcriptionalregulation in a papillary thyroid carcinoma model.MOL Cancer. 2006 Dec 11;5:70.

Centorrino F, Ballone A, Wolter M, Ottmann C. Biophysical and structural insight into the USP8/14-3-3 interaction. Send to FEBS Lett. 2018 Apr;592(7):1211-1220.

Chircop M. Rho GTPases as regulators of mitosis and cytokinesis in mammalian cells. Small GTPases. 2014;5. pii: e29770.

Cirak Y, Furuncuoglu Y, Yapicier O, Aksu A, Cubukcu E. Aurora A overexpression in breast cancer patients induces taxane resistance and results in worse prognosis. J BUON. 2015 Nov-Dec;20(6):1414-9.

Crane R, Gadea B, Littlepage L, Wu H, Ruderman JV. Aurora A, meiosis and mitosis. Biol Cell. 2004 Apr;96(3):215-29.

D'Assoro AB, Haddad T, Galanis E. Aurora-A Kinase as a Promising Therapeutic Target in Cancer. Front Oncol. 2016 Jan 6;5:295.

Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, Greenberg ME. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell. 2000 Jul;6(1):41-51.

Davidson B, Holth A, Wang Z, Hellsylt E, Tropé CG, Hetland Falkenthal TE, Holm R. Expression of 14-3-3 sigma and eta proteins is unrelated to survival in metastatic high-grade serous carcinoma. APMIS. 2018 Apr;126(4):309-313.

D'Avino PP, Giansanti MG, Petronczki M. Cytokinesis in animal cells. Cold Spring Harb Perspect Biol. 2015 Feb 13;7(4):a015834.

Davoli T, de Lange T. The causes and consequences of polyploidy in normal development and cancer. Annu Rev Cell Dev Biol. 2011;27:585-610.

Douglas ME, Davies T, Joseph N, Mishima M. Aurora B and 14-3-3 coordinately regulate clustering of centralspindlinduring cytokinesis. Curr Biol. 2010 May 25;20(10):927-33.

Du J, Chen L, Luo X, Shen Y, Dou Z, Shen J, Cheng L, Chen Y, Li C, Wang H, Yao X. 14-3-3zeta cooperates with phosphorylated Plk1 and is required for correctcytokinesis. Front Biosci (Schol Ed). 2012 Jan 1;4:639-50.

Ducat D, Zheng Y. Aurora kinases in spindle assembly and chromosome segregation.
Exp Cell Res. 2004 Nov 15;301(1):60-7.

Duensing A, Duensing S. Centrosomes, polyploidy and cancer. Adv Exp Med Biol. 2010;676:93-103.

Farag SS. The potential role of Aurora kinase inhibitors in haematological malignancies. Br J Haematol. 2011 Dec;155(5):561-79.

Ferrari S, Marin O, Pagano MA, Meggio F, Hess D, El-Shemerly M, Krystyniak A, Pinna LA. Aurora-A site specificity: a study with synthetic peptide substrates. Biochem J. 2005 Aug 15;390(Pt 1):293-302.

Fesquet D, De Bettignies G, Bellis M, Espeut J, Devault A. Binding of Kif23-iso1/CHO1 to 14-3-3 is regulated by sequential phosphorylations at two LATS kinase consensus sites. PLoS One. 2015 Feb 6;10(2):e0117857.

Francisco L, Wang W, Chan CS. Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation. Mol Cell Biol. 1994 Jul;14(7):4731-40.

Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 2005 Oct 13;437(7061):1043-7.

Ganem NJ, Storchova Z, Pellman D. Tetraploidy, aneuploidy and cancer.
Curr Opin Genet Dev. 2007 Apr;17(2):157-62.

Gao K, Zhang Y, Shi Q, Zhang J, Zhang L, Sun H, Jiao D, Zhao X, Tao H, Wei Y, Wang Y, Saiyin H, Zhao SM, Li Y, Zhang P, Wang C. iASPP-PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation. Cell Death Dis. 2018 May 9;9(5):528.

Gardino AK, Smerdon SJ, Yaffe MB. Structural determinants of 14-3-3 binding specificities and regulation of subcellular localization of 14-3-3-ligand complexes: a comparison of the X-ray crystal structures of all human 14-3-3 isoforms. Semin Cancer Biol. 2006 Jun;16(3):173-82.

Gautschi O, Heighway J, Mack PC, Purnell PR, Lara PN Jr, Gandara DR. Aurora kinases as anticancer drug targets. Clin Cancer Res. 2008 Mar 15;14(6):1639-48.

Gemoll T, Auer G, Ried T, Habermann JK. Genetic Instability and Disease Prognostication. Recent Results Cancer Res. 2015;200:81-94.

Giles N, Forrest A, Gabrielli B. 14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity. J Biol Chem. 2003 Aug 1;278(31):28580-7.

Glotzer M. Cytokinesis: centralspindlin moonlights as a membrane anchor. Curr Biol. 2013 Feb 18;23(4):R145-7.

Glotzer M. The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat Rev Mol Cell Biol. 2009 Jan;10(1):9-20.

Glover DM, Leibowitz MH, McLean DA, Parry H. Mutations in aurora prevent centrosome separation leading to the formationof monopolar spindles. Cell. 1995 Apr 7;81(1):95-105.

Guse A, Mishima M, Glotzer M. Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis. Curr Biol. 2005 Apr 26;15(8):778-86.

Hawse JR, Hejtmancik JF, Huang Q, Sheets NL, Hosack DA, Lempicki RA, Horwitz J, Kantorow M. Identification and functional clustering of global gene expression differences between human age-related cataract and clear lenses. Mol Vis. 2003 Oct 7;9:515-37.

Healy, A. M., S. Zolnierowicz, A. E. Stapleton, M. Goebl, A. A. DePaoli-Roach, and J. R. Pringle. 1991. CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2A protein phosphatase. Mol. Cell. Biol. 11:5767-5780.

Hidehiro Takahashi, Toshinari Iwata, Yoshinori Kitagawa, Reisuke H. Takahashi, Yuko Sato, Hideki Wakabayashi, Miwa Takashima, Hiroshi Kido, Kazuo Nagashima,Kimbra Kenney, Clarence J. Gibbs, Jr., and Takeshi Kurata. Increased Levels of ɛ and γ Isoforms of 14-3-3 Proteins in Cerebrospinal Fluid in Patients with Creutzfeldt-Jakob Disease. Clin Diagn Lab Immunol. 1999 Nov; 6(6): 983–985.

Hirota T, Kunitoku N, Sasayama T, Marumoto T, Zhang D, Nitta M, Hatakeyama K, Saya H. Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell. 2003 Sep 5;114(5):585-98.

Hornick JE, Karanjeet K, Collins ES, Hinchcliffe EH. Kinesins to the core: The role of microtubule-based motor proteins in building the mitotic spindle midzone. Semin Cell Dev Biol. 2010 May;21(3):290-9.

Huber SC, MacKintosh C, Kaiser WM. Metabolic enzymes as targets for 14-3-3 proteins. Plant Mol Biol. 2002 Dec;50(6):1053-63.

Hutterer A, Glotzer M, Mishima M. Clustering of centralspindlin is essential for its accumulation to the centralspindle and the midbody. Curr Biol. 2009 Dec 15;19(23):2043-9.

Iltzsche F, Simon K, Stopp S, Pattschull G, Francke S, Wolter P, Hauser S, Murphy DJ, Garcia P, Rosenwald A, Gaubatz S. An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma. Oncogene. 2017 Jan 5;36(1):110-121.

Isha Nasa, Arminja N. Kettenbach Coordination of Protein Kinase and Phosphoprotein Phosphatase Activities in Mitosis Front. Cell Dev. Biol., 22 March 2018.

Jeng YM, Peng SY, Lin CY, Hsu HC. Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res. 2004 Mar 15;10(6):2065-71.

Jiun-Ming Wu, Chiung-Tong Chen, Mohane Selvaraj Coumar, Wen-Hsin Lin, Zi-Jie Chen, John T.-A. Hsu, Yi-Hui Peng, Hui-Yi Shiao, Wen-Hsing Lin, Chang-Ying Chu, Jian-Sung Wu, Chih-Tsung Lin, Ching-Ping Chen, Ching-Cheng Hsueh, Kai-Yen Chang, Li-Pin Kao, Chi-Ying F. Huang, Yu-Sheng Chao, Su-Ying Wu, Hsing-Pang Hsieh, and Ya-Hui ChiAurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules. Proc Natl Acad Sci U S A. 2013 May 7; 110(19): E1779–E1787.

Jordan SN, Canman JC. Rho GTPases in animal cell cytokinesis: an occupation by the one percent. Cytoskeleton (Hoboken). 2012 Nov;69(11):919-30.

Joseph N, Hutterer A, Poser I, Mishima M. ARF6 GTPase protects the post-mitotic midbody from 14-3-3-mediated disintegration. EMBO J. 2012 May 30;31(11):2604-14.

Joukov V, Walter JC, De Nicolo A. The Cep192-organized aurora A-Plk1 cascade is essential for centrosome cycle and bipolar spindle assembly. Mol Cell. 2014 Aug 21;55(4):578-91.

Kaitna S, Mendoza M, Jantsch-Plunger V, Glotzer M. Incenp and an aurora-like kinase form a complex essential for chromosomesegregation and efficient completion of cytokinesis. Curr Biol. 2000 Oct 5;10(19):1172-81.

Karthigeyan D, Prasad SB, Shandilya J, Agrawal S, Kundu TK. Biology of Aurora A kinase: implications in cancer manifestation and therapy. Med Res Rev. 2011 Sep;31(5):757-93.

Kato T, Lee D, Wu L, Patel P, Young AJ, Wada H, Hu HP, Ujiie H, Kaji M, Kano S, Matsuge S, Domen H, Kaga K, Matsui Y, Kanno H, Hatanaka Y, Hatanaka KC, Matsuno Y, de Perrot M, Yasufuku K. Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma. Int J Oncol. 2016 Aug;49(2):448-56.

Khorrami A, Sharif Bagheri M, Tavallaei M, Gharechahi J. The functional significance of 14-3-3 proteins in cancer: focus on lung cancer. Horm Mol Biol Clin Investig. 2017 Aug 5;32(3).

Kilani RT, Maksymowych WP, Aitken A, Boire G, St-Pierre Y, Li Y, Ghahary A. Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation. J Rheumatol. 2007 Aug;34(8):1650-7.

Kitamura T, Kawashima T, Minoshima Y, Tonozuka Y, Hirose K, Nosaka T. Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation. Cell Struct Funct. 2001 Dec;26(6):645-51.

Lacroix B, Maddox AS. Cytokinesis, ploidy and aneuploidy. J Pathol. 2012 Jan;226(2):338-51.

Lam T, Thomas LM, White CA, Li G, Pone EJ, Xu Z, Casali P. Correction: Scaffold Functions of 14-3-3 Adaptors in B Cell Immunoglobulin Class Switch DNA Recombination. PLoS One. 2017 Mar 15;12(3):e0174195. doi: 10.1371/journal.pone.0174195. eCollection 2017.

Lee KY, Esmaeili B, Zealley B, Mishima M. Direct interaction between centralspindlin and PRC1 reinforces mechanicalresilience of the central spindle. Nat Commun. 2015 Jun 19;6:7290.

Lekomtsev S, Su KC, Pye VE, Blight K, Sundaramoorthy S, Takaki T, Collinson LM, Cherepanov P, Divecha N, Petronczki M. Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis. Nature. 2012 Dec 13;492(7428):276-9.

Li M, Gao K, Chu L, Zheng J, Yang J. The role of Aurora-A in cancer stem cells. Int J Biochem Cell Biol. 2018 May;98:89-92.

Liang Y, Liu M, Wang P, Ding X, Cao Y. Analysis of 20 genes at chromosome band 12q13: RACGAP1 and MCRS1 overexpression in nonsmall-cell lung cancer. Genes Chromosomes Cancer. 2013 Mar;52(3):305-15.

Lin HK, Wang G, Chen Z, Teruya-Feldstein J, Liu Y, Chan CH, Yang WL, Erdjument-Bromage H, Nakayama KI, Nimer S, Tempst P, Pandolfi PP. Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB. Nat Cell Biol. 2009 Apr;11(4):420-32.

Lu J, Guo H, Treekitkarnmongkol W, Li P, Zhang J, Shi B, Ling C, Zhou X, Chen T, Chiao PJ, Feng X, Seewaldt VL, Muller WJ, Sahin A, Hung MC, Yu D. 14-3-3zeta Cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelial-mesenchymal transition. Cancer Cell. 2009 Sep 8;16(3):195-207.

Luo J, Feng J, Lu J, Wang Y, Tang X, Xie F, Li W. Aberrant methylation profile of 14-3-3 sigma and its reduced transcription/expression levels in Chinese sporadic female breast carcinogenesis. Med Oncol. 2010 Sep;27(3):791-7.

Marumoto T, Zhang D, Saya H. Aurora-A - a guardian of poles. Nat Rev Cancer. 2005 Jan;5(1):42-50.

McLean JB, Moylan JS, Horrell EM, Andrade FH. Proteomic analysis of media from lung cancer cells reveals role of 14-3-3 proteins in cachexia. Front Physiol. 2015 Apr 28;6:136.

Meraldi Pa, Honda R, Nigg EA. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. EMBO J. 2002 Feb 15;21(4):483-92.

Meraldi Pb, Honda R, Nigg EA. Aurora kinases link chromosome segregation and cell division to cancersusceptibility. Curr Opin Genet Dev. 2004 Feb;14(1):29-36.

Merlo LM, Wang LS, Pepper JW, Rabinovitch PS, Maley CC. Polyploidy, aneuploidy and the evolution of cancer. Adv Exp Med Biol. 2010;676:1-13. Review.

Michaelson D, Abidi W, Guardavaccaro D, Zhou M, Ahearn I, Pagano M, Philips MR. Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division. J Cell Biol. 2008 May 5;181(3):485-96.

Moore B.W., Perez V.J., Carlson F.D. Physiological and Biochemical Aspects of Nervous Integration, Prentice-Hall, Englewood Cliffs, NJ (1967), pp. 343-359.

Mosieniak G, Sikora E. Polyploidy: the link between senescence and cancer. Curr Pharm Des. 2010;16(6):734-40.

Mudge J, Miller NA, Khrebtukova I, Lindquist IE, May GD, Huntley JJ, Luo S, Zhang L, van Velkinburgh JC, Farmer AD, Lewis S, Beavis WD, Schilkey FD, Virk SM, Black CF, Myers MK, Mader LC, Langley RJ, Utsey JP, Kim RW, Roberts RC, Khalsa SK, Garcia M, Ambriz-Griffith V, Harlan R, Czika W, Martin S, Wolfinger RD, Perrone-Bizzozero NI, Schroth GP, Kingsmore SF. Genomic convergence analysis of schizophrenia: mRNA sequencing revealsaltered synaptic vesicular transport in post-mortem cerebellum. PLoS One. 2008;3(11):e3625.

Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N. Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 1996 Oct 31;3(5):321-9, 341-54.

Nguyen HGa, Ravid K. Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins. J Cell Physiol. 2006 Jul;208(1):12-22. Review.

Nguyen HGb, Ravid K. Polyploidy: mechanisms and cancer promotion in hematopoietic and other cells. Adv Exp Med Biol. 2010;676:105-22.

Nigg EA. Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol. 2001 Jan;2(1):21-32.

Nishimura Y, Yonemura S. Centralspindlin regulates ECT2 and RhoA accumulation at the equatorial cortex during cytokinesis. J Cell Sci. 2006 Jan 1;119(Pt 1):104-14.

Nislow C, Lombillo VA, Kuriyama R, McIntosh JR. A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. Nature. 1992 Oct 8;359(6395):543-7.

Nomura M, Shimizu S, Sugiyama T, Narita M, Ito T, Matsuda H, Tsujimoto Y. 14-3-3 Interacts directly with and negatively regulates pro-apoptotic Bax. J Biol Chem. 2003 Jan 17;278(3):2058-65.

Ohashi S, Sakashita G, Ban R, Nagasawa M, Matsuzaki H, Murata Y, Taniguchi H, Shima H, Furukawa K, Urano T. Phospho-regulation of human protein kinase
Aurora-A: analysis using anti-phospho-Thr288 monoclonal antibodies. Oncogene. 2006 Dec 14;25(59):7691-702.

Ohishi T, Hirota T, Tsuruo T, Seimiya H. TRF1mediates mitotic abnormalities induced by Aurora-A overexpression. Cancer Res. 2010 Mar 1;70(5):2041-52.

Patel MP, Masood A, Patel PS, Chanan-Khan AA. Targeting the Bcl-2. Curr Opin Oncol. 2009 Nov;21(6):516-23.

Pavicic-Kaltenbrunner V, Mishima M, Glotzer M. Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex. Mol Biol Cell. 2007 Dec;18(12):4992-5003.

Petersen J, Paris J, Willer M, Philippe M, Hagan IM. The S. pombe aurora-related kinase Ark1 associates with mitotic structuresin a stage dependent manner and is required for chromosome segregation. J Cell Sci. 2001 Dec;114(Pt 24):4371-84.

Raptis S, Bapat B. Genetic instability in human tumors. EXS. 2006;(96):303-20.

Rios AC, Fu NY, Jamieson PR, Pal B, Whitehead L, Nicholas KR, Lindeman GJ, Visvader JE. Essential role for a novel population of binucleated mammary epithelial cells in lactation.Nat Commun. 2016 Apr 22;7:11400. doi: 10.1038/ncomms11400.

Ritt DA, Monson DM, Specht SI, Morrison DK. Impact of feedback phosphorylation and Raf heterodimerization on normal and mutant B-Raf signaling. Mol Cell Biol. 2010 Feb;30(3):806-19.

Sabino D, Brown NH, Basto R. Drosophila Ajuba is not an Aurora-A activator but is required to maintain Aurora-A at the centrosome. J Cell Sci. 2011 Apr 1;124(Pt 7):1156-66.

Saigusa S, Tanaka K, Mohri Y, Ohi M, Shimura T, Kitajima T, Kondo S, Okugawa Y, Toiyama Y, Inoue Y, Kusunoki M. Clinical significance of RacGAP1 expression at the invasive front of gastric cancer. Gastric Cancer. 2015 Jan;18(1):84-92.

Sardon T, Pache RA, Stein A, Molina H, Vernos I, Aloy P. Uncovering new substrates for Aurora A kinase. EMBO Rep. 2010 Dec;11(12):977-84.

Saurin AT, Durgan J, Cameron AJ, Faisal A, Marber MS, Parker PJ. The regulated assembly of a PKCepsilon complex controls the completion of cytokinesis. Nat Cell Biol. 2008 Aug;10(8):891-901.

Simpson AJ. Sequence-based advances in the definition of cancer-associated genemutations. Curr Opin Oncol. 2009 Jan;21(1):47-52.

Storchova Z, Kuffer C. The consequences of tetraploidy and aneuploidy. J Cell Sci. 2008 Dec 1;121(Pt 23):3859-66.

Storchova Z, Pellman D. From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol. 2004 Jan;5(1):45-54.

Sun H, Wang Y, Wang Z, Meng J, Qi Z, Yang G. Aurora-A controls cancer cell radio- and chemoresistance via ATM/Chk2-mediated DNA repair networks.Biochim Biophys Acta. 2014 May;1843(5):934-44.

Sun L, Zhang C, Yang Z, Wu Y, Wang H, Bao Z, Jiang T. KIF23 is an independent prognostic biomarker in glioma, transcriptionally regulated by TCF-4.
Oncotarget. 2016 Apr 26;7(17):24646-55.

Tatsumoto T, Xie X, Blumenthal R, Okamoto I, Miki T. Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis. J Cell Biol. 1999 Nov 29;147(5):921-8.

Tsai MY, Wiese C, Cao K, Martin O, Donovan P, Ruderman J, Prigent C, Zheng Y. A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindleassembly. Nat Cell Biol. 2003 Mar;5(3):242-8.

Tzivion G, Shen YH, Zhu J. 14-3-3 proteins; bringing new definitions to scaffolding. Oncogene. 2001 Oct 1;20(44):6331-8.

Tzivion G, Avruch J. 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation. J Biol Chem. 2002 Feb 1;277(5):3061-4.

Vader G, Lens SM. The Aurora kinase family in cell division and cancer. Biochim Biophys Acta. 2008 Sep;1786(1):60-72.

Venoux M, Basbous J, Berthenet C, Prigent C, Fernandez A, Lamb NJ, Rouquier S. ASAP is a novel substrate of the oncogenic mitotic kinase Aurora-A: phosphorylation on Ser625 is essential to spindle formation and mitosis. Hum Mol Genet. 2008 Jan 15;17(2):215-24.

Vikberg AL, Vooder T, Lokk K, Annilo T, Golovleva I. Mutation analysis and copy number alterations of KIF23 in non-small-celllung cancer exhibiting KIF23 over-expression. Onco Targets Ther. 2017 Oct 11;10:4969-4979.

Wadhwa N, Mathew BB, Jatawa SK, Tiwari A. Genetic instability in urinary bladder cancer: An evolving hallmark. J Postgrad Med. 2013 Oct-Dec;59(4):284-8.

Wang YC, Lee YH, Huang GC, Lin YH, Fan-Chiang MH, Chiu AW, Huang YL. Enhanced transformation and chemosensitivity of NIH3T3 cells transducedwith hepatoma up-regulated protein. Biochem Biophys Res Commun. 2006 Feb 3;340(1):244-9. Epub 2005 Dec 9.

Wang XX, Liu R, Jin SQ, Fan FY, Zhan QM.Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line. Cell Res. 2006 Apr;16(4):356-66.

Woodcock JM, Coolen C, Goodwin KL, Baek DJ, Bittman R, Samuel MS, Pitson SM, Lopez AF. Destabilisation of dimeric 14-3-3 proteins as a novel approach to anti-cancer therapeutics. Oncotarget. 2015 Jun 10;6(16):14522-36.

Wu CG, Chen H, Guo F, Yadav VK, Mcilwain SJ, Rowse M, Choudhary A, Lin Z, Li Y, Gu T, Zheng A, Xu Q, Lee W, Resch E, Johnson B, Day J, Ge Y, Ong IM, Burkard ME, Ivarsson Y, Xing Y. PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis. Cell Discov. 2017 Aug 8;3:17027.

Yan M, Wang C, He B, Yang M, Tong M, Long Z, Liu B, Peng F, Xu L, Zhang Y, Liang D, Lei H, Subrata S, Kelley KW, Lam EW, Jin B, Liu Q. Aurora-A Kinase: A Potent Oncogene and Target for Cancer Therapy. Med Res Rev. 2016 Nov;36(6):1036-1079.

Ye AA, Torabi J, Maresca TJ. Biol Bull. Aurora A Kinase Amplifies a Midzone Phosphorylation Gradient to Promote High-Fidelity Cytokinesis.
2016 Aug;231(1):61-72.

Yeang CH, McCormick F, Levine A. Combinatorial patterns of somatic gene mutations in cancer. FASEB J. 2008 Aug;22(8):2605-22.

Ye L, Li H, Zhang F, Lv T, Liu H, Song Y. [Expression of KIF23 and Its Prognostic Role in Non-small Cell Lung Cancer: 
Analysis Based on the Data-mining of Oncomine]. Zhongguo Fei Ai Za Zhi. 2017 Dec 20;20(12):822-826.

Youlden DR, Cramb SM, Baade PD. The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol. 2008 Aug;3(8):819-31.

Yu CT, Hsia JY, Hseih YC, Su LJ, Lee TC, Ku CF, Chen KS, Chen JM, Wei TY, Lee YC, Huang CY, Wu YC, Yang CY, Hsu SL. The novel protein suppressed in lung cancer down-regulated in lung cancer tissues retards cell proliferation and inhibits the oncokinase Aurora-A. J Thorac Oncol. 2011 Jun;6(6):988-97.

Yu JX, Sieuwerts AM, Zhang Y, Martens JW, Smid M, Klijn JG, Wang Y, Foekens JA. Pathway analysis of gene signatures predicting metastasis of node-negativeprimary breast cancer. BMC Cancer. 2007 Sep 25;7:182.

Zhang D, Hirota T, Marumoto T, Shimizu M, Kunitoku N, Sasayama T, Arima Y, Feng L, Suzuki M, Takeya M, Saya H. Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models. Oncogene. 2004 Nov 18;23(54):8720-30.

Zurita M, Lara PC, del Moral R, Torres B, Linares-Fernández JL, Arrabal SR, Martínez-Galán J, Oliver FJ, Ruiz de Almodóvar JM. Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis. BMC Cancer. 2010 May 20;10:217.

電子全文 電子全文(網際網路公開日期:20230628)
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔