進階搜尋


 
系統識別號 U0026-0812200912054790
論文名稱(中文) SUMOylation 對於Sp1轉錄活性的影響
論文名稱(英文) The effect of SUMOylation in the transcriptional activity of Sp1
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 94
學期 2
出版年 95
研究生(中文) 鍾雅旬
研究生(英文) Yu-Hsun Chung
電子信箱 s2693401@mail.ncku.edu.tw
學號 s2693401
學位類別 碩士
語文別 中文
論文頁數 90頁
口試委員 口試委員-洪建中
指導教授-黃金鼎
口試委員-張文昌
中文關鍵字 後轉錄修飾  類泛素化 
英文關鍵字 posttranscriptional modification  Sp1  SUMOylation 
學科別分類
中文摘要 摘要

Sp1為遍佈於體內並且調控許多哺乳類動物基因的轉錄因子,經由直接結合或是recruit其他轉錄因子至目標基因啟動子的GC-rich區域方式以調控基因的轉錄活性。之前有文獻指出,Sp1具有許多不同的後轉錄修飾作用,如磷酸化、糖化及乙醯化但沒有類泛素化。我們實驗室以生物資訊軟體SUMOplotTM分析結果得知Sp1具有高度會被SUMO-1修飾的區域,即VKIE。我們建構Sp1突變子(K→R),並經由實驗證實,Sp1具有SUMOylation而Sp1(K9R)則否。另外,當細胞處裡NEM(SUMO水解抑制劑)的情況下,可在較高分子量的位置觀察到內生性的SUMO-1-Sp1。由此可知,in vitro或in vivo皆可觀察到Sp1會被SUMO-1修飾,而且lysine residue 9對於Sp1 SUMOylation是重要且必要的。在基因調控方面,移除這個SUMOylated site則會增加p21Waf1/Cip1轉錄活性的作用,所以觀察到Sp1(K9R)比Sp1-wt具有更高的轉錄活性。有趣的是,相較於Sp1我們發現無法被SUMO-1修飾的Sp1(K9R)會recruit更多p300。但是這些現象可能是因為Sp1(K9R)蛋白質表現量較Sp1蛋白質穩定所造成的結果。由於發現蛋白質表現量不同,所以接下來我們便觀察到當細胞處理MG132的情況之下Sp1-wt比沒有處理MG132的Sp1-wt其Ubiquitination較明顯,可以在較高分子量的位置發現到許多單一-或poly-Ubiquitin-Sp1 bands。因此我們認為SUMO-1和ubiquitin之間可能處於相互競爭的狀態。除此之外,Sp1在細胞下核內的分佈情形並不會因為SUMO修飾而改變,此現象在不同的細胞週期方面亦然。由此可知,此項研究提出一種創新的機轉來探討SUMO在p21 Waf1/Cip1的表現上之角色。過去研究傾向SUMO對於p21表現是扮演負向調控,因為將會被SUMO修飾的位置(K9)置換則會造成p21 Waf1/Cip1表現增加。但本篇研究顯示這個位置同樣是Ubiquitination的位置,於是我們認為SUMO會來和ubiquitin競爭K9而來穩定Sp1,藉由Sp1的穩定來增加p21 Waf1/Cip1表現。因此,我們認為SUMO對p21 Waf1/Cip1可能扮演一個正向調控的角色。



英文摘要 Abstract

The transcription factor Sp1 is a ubiquitously expressed member of the Sp family of transcription factor that is involved in the expression and regulation of many genes. Previous studies showed that Sp1 is highly phosphorylated, acetylated and glycosylated but not sumoylated. Our lab using SUMOplotTM prediction software found that Sp1 contains one SUMO targeted motifs, VKIE, with high probability within the first 28 amino acids. Therefore we wanted to study whether Sp1 could be SUMOylated. We constructed a Sp1 mutant form(VKIE→ VRIE), and found Sp1-WT could be SUMOylated but not Sp1(K9R) mutant form. Furthermore, Western Blot analysis revealed a high molecular weight SUMO-Sp1 in A431 cells endogenously. In vitro and in vivo, Western Blot analysis revealed that Sp1 can be sumoylated at lysine 9. Besides, we also found that the transcriptional activity of p21 Waf1/Cip1 was more active when transfected with Sp1(K9R) than with Sp1 WT. This data represent that this residue is important for the expression of p21 Waf1/Cip1. To study the mechanism, we found that the recruitment of p300 by Sp1(K9R) was increased than that by Sp1. However, we also found that the level of Sp1(K9R) was also higher than that of Sp1. On the other hand, when treated cells with MG132(26S proteosome inhibitor)we found mono- or poly-ubiquitin-Sp1 bands in high molecular weight. Therefore, we considered that it is likely resulted from competition for the same conjugating lysine site between SUMO-1 and ubiquitin. Furthermore, here we also found that the subcellular localization of Sp1 is not altered upon SUMO modification as well as in different cell cycle. These data provide new mechanism to investigate the role of SUMO in the expression of p21 Waf1/Cip1. Many Previously functional studies showed that SUMOylation negatively regulated p21 Waf1/Cip1 activity, and Sp1(K9R) can increase the transcriptional activity of p21 Waf1/Cip1. But here we found that this lysine site could also be ubiquitinated. Therefore, we hypothesized that SUMO can compete lysine 9 with ubiquitin to stabilize Sp1 and then to increase p21 Waf1/Cip1 activity. Our results suggest that SUMO may positively regulate the transcriptional activity of p21 Waf1/Cip1.



論文目次 目錄
目錄…………………………………………………………………… I
表目錄…………………………………………………………………II
圖目錄…………………………………………………………………III
中文摘要………………………………………………………………1
英文摘要………………………………………………………………3
縮寫檢索表……………………………………………………………5
第一章 緒論………………………………………………………6
第二章 實驗材料…………………………………………………15
第三章 實驗方法…………………………………………………20
第四章 實驗結果……………………………………………………38
第一節 探討Sp1轉錄因子的氨基端是否具有SUMOylation現象
第二節 探討Sp1轉錄因子的SUMOylation對基因調控的影響
第三節 探討Sp1變異子與野生型在細胞下核內的分佈情形
第四節 進一步探討受SUMO影響的蛋白質為何
第五章 總結與討論…………………………………………………49
第六章 參考文獻……………………………………………………56
附圖………………………………………………………………… 67
附表………………………………………………………………….80
附錄………………………………………………………………….81



圖目錄
Fig.1 One predicted SUMO acceptor site within amino terminus of Sp1 by SUMOplot program------68
Fig.2 Sp1 is SUMOylated in vitro.-----------69
Fig.3 Sp1 is sumo modified in vivo.---------70
Fig.4 Sumoylation may positive regulateSp-dependent transcriptional capacity.------------71
Fig.5 The effect of Ubiquitination between Sp1-wt and Sp1-K9R-----------------------------72
Fig.6 The relationship between SUMOylation and Ubiquitination in interphase and M phase.--73
Fig.7 The relationship between HA-Sp1-wt or HA-Sp1-K9R and p300. --------------------------74
Fig.8 Subcellular localization of Sp1 or corresponding SUMOylation-deficient mutant K9R in A431 cells.---------------------------------75
Fig.9 Subcellular localization of pCDNA3.0-HA-Sp1-wt and SUMOylation- deficient mutant pCDNA3.0-HA-Sp1(K9R) in A431 cells under thymidine treatment at different cell cycle stages.----------------------------------------76
Fig.10 The difference between mock, Sp1 and K9R in 2D gel.---------------------------------77
Fig.11 A strategy for the generation of sumoylated proteins in E. coli.----------------78
Fig.12 A model of posttranslational competition for lysine 9 governs Sp1
stabilization.---------------------------------79


表目錄

Table 1 The sites were identified as potential post-translational modification of Sp1. ------81

附錄目錄
附錄1 Structural motifs in Sp factors. ----82
附錄2 The Btd and Sp boxes are conserved in Sp1-8.----------------------------------------83
附錄3 Sequence alignment of the zinc-finger domains of Sp1-like protein family members. --84
附錄4 The zinc fingers of Sp1-like transcription factors. -----------------------85
附錄5 In Sp2, the important histidine residue within the first zinc finger is replaced by a leucine residue. -----------------------------86
附錄6 Conjugation pathway of ubiquitin and the ubiquitin-like modifier SUMO--------------87
附錄7 Comparison of SUMO and ubiquitin and the SUMO conjugating pathway.-----------------88
附錄8 Two models for the effects of SUMO-modification of transcription factor activity.-89
參考文獻 第六章 參考文獻
Abdel-Hafiz, H., Takimoto, G.S., Tung, L., and Horwitz, K.B. The inhibitory function in human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression. J. Biol. Chem. 277, 33950-33956 (2002).
Abdelrahim M., Baker CH., Abbruzzses JL., Safe S. Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J Natl Cancer Inst. 98(12):855-68. (2006)
Armstrong, S. A., Barry, D. A., Leggett, R. W., and Mueller, C. R. Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. J. Biol. Chem. 272, 13489-13495 (1997).
Bakovic, M., Waite, K.A., and Vance, D.E. Functional significance of Sp1, Sp2, and Sp3 transcription factors in regulation of the murine CTP: phosphocholine cytidylyltransferase alpha promoter. J. Lipid Res. 41, 583-594 (2000).
Billon, N., Carlisi, D., Datto, M.B., et al. Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF/CIP1 during NGF- mediated neuronal differentiation. Oncogene 18, 2872-2882 (1999).
Black, A. R., Black, J. D., and Azizkhan-Clifford, J. Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J. Cell. Physiol. 188, 143–160 (2001)
Blake, M. C., Jambou, R. C., Swick, A. G., Kahn, J. W., and Azizkhan, J. C. Transcriptional initiation is controlled by upstream GC-box interactions in a TATAA-less promoter. Mol. Cell. Biol. 10, 6632- 6641 (1990).
Bouwman, P. and Philipsen, S. Regulation of the activity of Sp1 - related transcription factors. Mol. Cell. Endocrinol., 195, 27-38 (2002).
Brandeis, M., Frank, D., Keshet, I., Siegfried, Z., Mendelsohn, M., Nemes, A., Temper, V., Razin, A., and Cedar, H. Sp1 elements protect a CpG island from de novo methylation. Nature 371, 435-438 (1994).
Briggs, M. R., J. T. Kadonaga, S. P. Bell, and R. Tjian. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science 234, 47-52 (1986).
Chen, L. I., Nishinaka, T., Kwan, K., Kitabayashi, I., Yokoyama, K., Fu, Y. H., Grunwald, S., and Chiu, R. The retinoblastoma gene product RB stimulates Sp1-mediated transcription by liberating Sp1 from a negative regulator. Mol. Cell. Biol. 14, 4380-4389 (1994).
Chen, S.J., Artlett, C.M., Jimenez, S.A., and Varga, J. Modulation of human alphal (I) procollagen gene activity by interaction with Sp1 and Sp3 transcription factors in vitro. Gene 215, 101-110 (1998).
Chun, R. F., Semmes, O. J., Neuveut, C., and Jeang, K. T. Modulation of Sp1 phosphorylation by human immunodeficiency virus type 1 Tat. J. Virol. 72, 2615-2629 (1998).
Courey, A.J. and Tjian, R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell, 55, 887-898 (1988).
Courey, A.J., Holtzman, D.A., Jackson, S.P. and Tjian, R. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell, 59, 827-836 (1989).
Desterro, J.M.P., Rodriguez, M.S., and Hay, R.T. SUMO-1 modification of IB inhibits NF-B activation. Mol. Cell. 2, 233-239 (1998).
Datta, P.K., Raychaudhuri, P., Bagchi, S.Association of p107 with Sp1: genetically separable regions of p107 are involved in regulation of E2F- and Sp1-dependent transcription. Mol. Cell. Biol. 15, 5444–5452. (1995).
Doetzlhofer, A., Rotheneder, H., Lagger, G., Koranda, M., Kurtev, V., Brosch, G., Wintersberger, E., and Seiser, C. Histone Deacetylase 1 can repress transcription by binding to Sp1. Mol. Cell. Biol. 19, 5504-5511 (1999).
Dynan, W.S. and Tjian, R. Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell, 32, 669-680 (1983a).
Dynan, W.S. and Tjian, R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell, 35, 79-87 (1983b).
Erica S. Johnson. Protein modification by SUMO. Annu. Rev. Biochem. 73, 355-382(2004).
Eric R. M., Patricia A. M., Akiko S., and Juanita L. M. Epidermal growth factor and okadaic acid stimulate Sp1 proteolysis. J. Biol. Chem. 272, 16540- 16547 (1997).
Eaton, E.M. and Sealy, L. Modification of CCAAT/enhancer- binding protein- by the small ubiquitin-like modifier (SUMO) family members, SUMO-2 and SUMO-3. J. Biol. Chem. 278, 33416- 33421 (2003).
Fairall, L., Schwabe, J.W., Champman, L., Finch, J.T., and Rhodes, D. The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zine-finger/DNA recognitin. Nature, 366, 483-487 (1993).
Fojas de Borja, P., Collins, N. K., Du, P., Azizkhan-Clifford, J., and Mudryj, M. Cyclin A-CDK phosphorylates Sp1 and enhances Sp1-mediated transcription. EMBO J. 20, 5737-5747 (2001).
Freiman, R.F. and Tjian, R. Regulating the regulators: Lysine modifications make their mark. Cell 112, 11-17 (2003).
Gill, G. Post-translational modification by the small ubiquitin-related modifier SUMO has big effects on transcription factor activity. Curr. Opin. Genet. Dev. 13, 108-113 (2003).
Goodson, M.L., Hong, Y., Rogers, R., Matunis, M.J., Park-Sarge, O.-K. and Sarge, K.D. SUMO-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor. J. Biol. Chem. 276, 18513-18518 (2001).
Hagen, G., Muller, S., Beato, M. and Suske, G. Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes. Nucleic Acids Res., 20, 5519-5525 (1992).
Hagen, G., Mller, S., Beato, M., and Suske, G. Sp1-mediated transcriptional activation is repressed by Sp3. EMBO J. 13, 3843-3851 (1994).
Hagen, G., Dennig, J., Preiss, A., Beato, M. and Suske, G. Functional analyses of the transcription factor Sp4 reveal properties distinct from Sp1 and Sp3. J. Biol. Chem., 270, 24989-24994 (1995).
Harrison, S.M., Houzelstein, D., Dunwoodie, S.L., Beddington, R.S. Sp5, a new member of the Sp1 family, is dynamically expressed during development and genetically interacts with Brachyury. Dev. Biol. 227, 358-372 (2000).
Hoey, T., Weinzierl, R.O., Gill, G., Chen, J.L., Dynlacht, B.D., and Tjian, R. Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators. Cell 72, 247-260 (1993).
Hong, Y., Rogers, R., Matunis, M.J., Mayhew, C.N., Goodson, M., Park-Sarge, O.-K. and Sarge, K.D. Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification. J. Biol. Chem. 276, 40263-40267 (2001).
Huang, W., Zhao, S., Ammanamanchi, S., Brattain, M., Venkatasubbarao, K., and Freeman, J. W. Trichostatin A Induces Transforming Growth Factor Type II Receptor Promoter Activity and Acetylation of Sp1 by Recruitment of PCAF/p300 to a Sp1•NF-Y Complex. J. Biol. Chem. 280, 10047–10054 (2005)
Iniguez-Lluhi, J.A., and Pearce, D. A common motif within the negative regulatory regions of multiple factors inhibits their transcriptional synergy. Mol. Cell. Biol., 20, 6040-6050 (2000).
Jolliff, K., Li, Y., and Johnson, L. F. Multiple protein-DNA interactions in the TATAA-less mouse thymidylate synthase promoter. Nucleic Acids Res. 19, 2267-2274 (1991).
Kaczynski, J., Cook, T., Urrutia, R. Sp1- and Krppel-like transcription factors. Genome Biology, 4, 206 (2003).
Kadonaga, J.T., Carner, K.R., Masiarz, F.R. and Tjian, R. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell, 51, 1079-1090 (1987).
Kaihong Su, Mark D. Roos, Xiaoyong Yang, Innoc Han, Andrew J. Paterson, and Jeffrey E. Kudlow. An N-terminal region of Sp1 targets its proteasome-dependent degradation in vitro. J. Biol. Chem. 274, 15194-15202 (1999).
Karlseder, J., Rotheneder, H., and Wintersberger, E. Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. Mol.Cell. Biol. 16, 1659-1667 (1996).
Kim, S. J., Onwuta, U. S., Lee, Y. I., Li, R., Botchan, M. R., and Robbins, P. D. The retinoblastoma gene product regulates Sp1-mediated transcription. Mol. Cell. Biol. 12, 2455-2463 (1992).
Kingsley, C. and Winoto, A. Cloning of GT box-binding proteins: a novel Sp1 multigene family regulating T-cell receptor gene expression. Mol. Cell. Biol., 12, 4251-4261 (1992).
Lee, J. A., Suh, D. C., Kang, J. E., Kim, M. H., Park, H., Lee, M. N., Kim, J. M., Jeon, B. N., Roh, H. E., Yu, M. Y., Choi, K. Y., Kim, K. Y., and Hur, M. W. Transcriptional activity of Sp1 is regulated by molecular interactions between the Zinc finger DNA binding domain and the inhibitory domain with corepressors, and this interaction is modulated by MEK. J. Biol. Chem. 280, 28061–28071 (2005)
Lee, J. S., Galvin, K. M., and Shi, Y. Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1. Proc. Natl. Acad. Sci. USA 90, 6145-6149 (1993).
Lee Y.H., Yano M., Liu S.Y., Matsunaga. E., Johnson P.F., and Gonzalez F.J. A novel cis-acting element controlling the rat CYP2D5 gene and requiring cooperativity between C/EBP and a Sp1 factor. Mol. Cell. Biol. 14, 1383-1394 (1994).
Lee Y.H., Williams, S.M., Bear, M., Sterneck, E., Gonzalez, F.J., and Johnson, P.F. The ability of C/EBP but not C/EBP to synergize with an Sp1 protein is specified by the leucine zipper and activation domain. Mol. Cell. Biol. 17, 2038-2047 (1997).
Lin, L., and Ghosh, S. A glycine-rich region in NF-B p105 function as a processing signal for the generation of the p50 subunit. Mol. Cell. Biol. 16, 2248-2254 (1996).
Lin, S. Y., Black, A. R., Kostic, D., Pajovic, S., Hoover, C. N., and Azizkhan, J. C. Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction. Mol. Cell. Biol. 16, 1668 - 1675 (1996).
Liao, W. C., Geng, Y., and Johnson, L. F. In vitro transcription of the TATAA-less mouse thymidylate synthase promoter: multiple transcription start points and evidence for bidirectionality. Gene 146, 183-189 (1994).
Lu, J., Lee, W., Jiang, C., and Keller, E. B. Start site selection by Sp1 in the TATA-less human Ha-ras promoter. J. Biol. Chem. 269, 5391-5402 (1994).
Macleod, D., Charlton, J., Mullins, J., and Bird, A. P. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev. 8, 2282-2292 (1994).
Maen Abdelrahim and Stephen Safe. Cyclooxygenase-2 inhibitors decrease vascular endothelial growth factor expression in colon cancer cells by enhanced degradation of Sp1 and Sp4 proteins. Mol. Pharmacol. 68(2):317-29 (2005)
Maniatis, T., Goodbourn, S., and Fischer, J. A. Regulation of inducible and tissue-specific gene expression. Science 236, 1237-45 (1987).
Marin, M., Karis, A., Visser, P., Grosveld, F. and Philipsen, S. Transcription factor Sp1 is essential for early embryonic develop- ment but dispensable for cell growth and differentiation. Cell, 89, 619-628 (1997).
Mary L. Spengler and Michael G. Brattain. Sumoylation inhibits cleavage of Sp1 N-terminal negative regulatory domain and inhibits Sp1-dependent transcription. J. Cell. Biol. 281, 5567-5574 (2006)
Mastrangelo, I.A., Courey, A.J., Wall, J.S., Jackson, S.P. and Hough, P.V. DNA looping and Sp1 multimer links: a mechanism for transcriptional synergism and enhancement. Proc. Natl. Acad. Sci. USA, 88, 5670-5674 (1991).
Matunis, M.J., Wu, J. and Blobel, G. SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex. J. Cell. Biol. 140, 499-509 (1998).
McKnight, S., and Tjian, R. Transcriptional selectivity of viral genes in mammalian cells. Cell 46, 795-805 (1986).
Milanini-Mongiat, J., Pouyssegur, J., and Pages, G. Identification of two Sp1 phosphorylation sites for p42/p44 mitogen- activated protein kinases: their implication in vascular endothelial growth factor gene transcription. J. Biol. Chem. 277, 20631-20639 (2002).
Mink, S., Haenig, B. and Klempnauer, K.-H. Interaction and functional collaboration of p300 and C/EBP. Mol. Cell. Biol. 17, 6609- 6617 (1997).
Mller, S., Hoege, C., Pyrowolakis, G., and Jentsch, S. SUMO, ubiquitin's mysterious cousin. Nature Rev. Mol. Cell Biol.2, 202-210 (2001).
Murata Y., Kim H.G., Rogers K.T., Udvadia A.J., and Horowitz J.M. Negative regulation of Sp1 trans-activation is correlated with the binding of cellular proteins to the amino terminus of the Sp1 trans- activation domain. J. Biol. Chem. 269, 20674-20681 (1994).
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J.M., Behringer, R.R. and de Crombrugghe, B. The novel zinc finger- containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell, 108, 17-29 (2002).
Nishinnaka, T., Fu, Y.H., Chen, L.I., Yokoyama, K., and Chiu, R. An unique cathepsin-like protease isolated from CV-1 cells is involved in rapid degradation of retinoblastoma susceptibility gene product RB, and transcription factor Sp1. Biochim. Biophys. Acta.. 1351, 274 -286 (1997).
Ogra, Y., Suzuki, K., Gong, P., Otsuka, F., and Koizumi, S. Negative regulatory role of Sp1 in metal responsive element-mediated transcriptional activation. J. Biol. Chem. 276, 16534-16539 (2001).
Pal, S., Claffey, K. P., Cohen, H. T., and Mukhopadhyay, D. Activation of Sp1-mediated vascular permeability factor/vascular endothelial growth factor transcription requires specific interaction with protein kinase C ζ. J. Biol. Chem. 273, 26277-26280 (1998).
Pascal, E. and Tjian, R. Different activation domains of Sp1 govern formation of multimers and mediate transcriptional synergism. Genes Dev. 5, 1646-1656 (1991).
Pavletich, N.P., and Pabo, C.O. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1. Science 252, 809-817 (1991).
Perkins, N. D., Agranoff, A. B., Pascal, E., and Nabel, G. J. An interaction between the DNA-binding domains of RelA (p65) and Sp1 mediates human immunodeficiency virus gene activation. Mol. Cell. Biol. 14, 6570-6583 (1994).
Persengiev, S.P., Saffer, J.D., and Kilpatrick D.L. An alternatively spliced form of the transcription factor Sp1 containing only a single glutamine-rich transactivation domain. Proc. Natl. Acad. Sci. USA 92, 9107-9111 (1995).
Pugh, B. F., and Tjian, R. Transcription from a TATA-less promoter requires a multisubunit TFIID complex. Genes Dev. 5, 1935–1945 (1991)
Roeder, R.G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem. Sci., 16, 402-408 (1991).
Rodriguez, M.S., Dargemont, C. and Hay, R.T. SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. J. Biol. Chem., 276, 12654-12659 (2001).
Rohlff, C., Ahmad, S., Borellini, F., Lei, J., and Glazer, R. I. Modulation of transcription factor Sp1 by cAMP-dependent protein kinase. J. Biol. Chem. 272, 21137-21141 (1997).
Roos, M. D., Su, K., Baker, J. R., and Kudlow, J. E. O-glycosylation of an Sp1-derived peptide blocks known Sp1 protein interactions. Mol. Cell. Biol. 17, 6472-6480 (1997).
Rotheneder, H., Geymayer, S., and Haidweger, E. Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter. J. Mol. Biol. 293, 1005-1015 (1999).
Ryu, S., Zhou, S., Ladurner, A. G., and Tjian, R. The transcriptional cofactor complex CRSP is required for activity of the enhancer binding protein Sp1. Nature 397, 446-50 (1999).
Saffer, J.D., Jackson, S.P., and Annarella, M.b. Developmental expression of Sp1 in the mouse. Mol. Cell. Biol. 11, 2189-2199 (1991).
Sapetsching, A., Rischitor, G., Braun, H., Doll, A., Schergaut, M., Melchior, F., and Suske, G. Transcription factor Sp3 is silenced through SUMO modification by PIAS1. EMBO J. 21, 5206-5215 (2002).
Sapetschnig, A., Koch, F., Rischitor, G., Mennenga, T., and Suske, G. Complexity of translationally controlled transcription factor Sp3 isoform expression. J. Biol. Chem. 279, 42095–42105 (2004)
Serfling, E., Lubbe, A., Dorsch-Hasler, K., and Schaffner, W. Metal- dependent SV40 viruses containing inducible enhancers from the upstream region of metallothionein genes. EMBO J. 4, 3851-3859 (1985).
Scohy, S., Gabant, P., Van Reeth, T., Hertveldt, V., Dreze, P.L., Van Vooren, P., Riviere, M., Szpirer, J. and Szpirer, C. Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family. Genomics, 70, 93-101 (2000).
Shao, Z., and Robbins, P. D. Differential regulation of E2F and Sp1- mediated transcription by G1 cyclins. Oncogene 10, 221-228 (1995).
Shihua He and James R. Davie*. Sp1 and Sp3 foci distribution throughout mitosis. Journal of Cell Science 119, 1063-1070 (2006).
Shiio, Y., and Eisenman, R. N. Histone sumoylation is associated with transcriptional repression. Proc. Natl. Acad. Sci. U. S. A. 100, 13225–13230 (2003)
Shou, Y., Baron, S., and Poncz, M. An Sp1-binding silencer element is a critical negative regulator of the megakaryocyte-specific alphaIIb gene. J. Biol. Chem. 273, 5716-26 (1998).
Spengler, M. L., Kennett, S. B., Moorefield, K. S., Simmons, S. O., Brattain, M. G., and Horowitz, J. M. Sumoylation of internally initiated Sp3 isoforms regulates transcriptional repression via a Trichostatin A-insensitive mechanism. Cell. Signal. 17, 153–166 (2005)
Su, K., Roos, M.D., Yang, X., Han, I., Paterson, A.J., and Kudlow J.E. An N-terminal region of Sp1 targets its proteasome- dependent degradation in Vitro. J. Biol. Chem. 274, 15194-15202 (1999).
Subramanian, L., Benson, M.D., and Iniguez-Lluhi, J.A. A synergy control motif within the attenuator domain of CCAAT/enhancer- binding protein  inhibits transcriptional synergy through its PIASy enhanced modification by SUMO-1 or SUMO-3. J. Biol.Chem. 278, 9134-9141 (2003).
Supp, D.M., Witte, D.P., Branford, W.W., Smith, E.P., and Potter, S.S. Sp4, a member of the Sp1-family of zinc finger transcription factors, is required for normal murine growth, viability, and male fertility. Dev. Biol. 176, 284-299 (1996).
Suske, G. The Sp-family of transcription factors. Gene 238, 291-300 (1999).
Suzuki, T., Kimura, A., Nagai, R. and Horikoshi, M. Regulation of interaction of the acetyltransferase region of p300 and the DNA- binding domain of Sp1 on and through DNA binding. Genes to Cell 5, 29-41 (2000).
Takahara, T., Kanazu, S.I., Yanagisawa, S., Akanuma, H. Heterogeneous Sp1 mRNAs in human HepG2 cells include a product of homotypic trans-splicing. J. Biol. Chem. 275, 38067-38072 (2000).
Tang, Q. Q., Jiang, M. S., and Lane, M. D. Repressive effect of Sp1 on the C/EBPalpha gene promoter: role in adipocyte differentiation. Mol. Cell. Biol. 19, 4855-4865 (1999).
Treichel, D., Becker, M.B., Gruss, P. The novel transcription factor gene Sp5 exhibits a dynamic and highly restricted expression pattern

during mouse embryogenesis. Mech. Dev. 101, 175-179 (2001).
Tzeng S.J., and Huang J.D. Transcriptional regulation of the rat Mrp3 promoter in intestine cells. Biochem. Biophys. Res. Commun.291, 270-277 (2002).
Udvadia, A. J., Rogers, K. T., Higgins, P. D., Murata, Y., Martin, K. H., Humphrey, P. A., and Horowitz, J. M. Sp1 binds promoter elements regulated by the RB protein and Sp1 mediated transcription is stimulated by RB coexpression. Proc. Natl. Acad. Sci. U S A 90, 3265-3269 (1993).
Udvadia, A. J., Templeton, D. J., and Horowitz, J. M. Functional interactions between the retinoblastoma (Rb) protein and Sp- family members: superactivation by Rb requires amino acids necessary for growth suppression. Proc. Natl. Acad. Sci. U S A 92, 3953-3957 (1995).
Verger, A., Perdomo, J., and Crossley, M. Modification with SUMO: A role in transcriptional regulation. EMBO Rep. 4, 137-142 (2003)
Zaid, A., Hodny, Z., Li, R., Nelson, B.D. Sp1 acts as a repressor of the human adenine nucleotide translocase-2 (ANT2) promoter. Eur. J. Biochem. 268, 5497-5503 (2001).
Zenzie-Gregory, B., Khachi, A., Garraway, I. P., and Smale, S. T. Mechanism of initiator-mediated transcription: evidence for a functional interaction between the TATA-binding protein and DNA in the absence of a specific recognition sequence. Mol. Cell. Biol. 13, 3841-3849 (1993).
Zheng, X. L., Matsubara, S., Diao, C., Hollenberg, M. D., and Wong, N. C. Epidermal growth factor induction of apolipoprotein A-I is mediated by the Ras-MAP kinase cascade and Sp1. J. Biol. Chem. 276, 13822-9 (2001).
Zhong, S., Salomoni, P., and Pandolfi, P.P. The transcriptional role of PML and the nuclear body. Nature Cell Biol. 2, E85-E90 (2000).
Zwicker, J., Liu, N., Engeland, K., Lucibello, F. C., and Muller, R. Cell cycle regulation of E2F site occupation in vivo. Science 271, 1595-1597 (1996)
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2016-08-10起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2011-08-10起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw