SUMO-1對p53基因誘導HepG2細胞凋亡的增強作用_《中國普外基礎與臨床雜志》

作者：

盧星榕 , 易繼林

華中科技大學同濟醫學院附屬同濟醫院普外科(武漢430030);

關鍵詞：

小分子泛素樣修飾體-1 p53基因鼠雙微粒體基因2 HepG2細胞凋亡

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【摘要】目的研究小分子泛素樣修飾體-1(small ubiquitin-like modifier-1，SUMO-1)在野生型p53基因誘導HepG2細胞凋亡中的作用。
方法用含人野生型p53基因質粒pcDNA3-wtp53(pwtp53)、含人雙微粒體基因2〔（human double minute gene 2 (HDM2)；鼠同源基因為MDM2〕質粒pCMV-HDM1B(pMDM2)、含人SUMO-1基因質粒pcDNA3-His6-SUMO-1(pSUMO-1)和空質粒pcDNA3分別或同時轉染HepG2細胞，獲得各轉染細胞系，應用Western blot檢測轉染后細胞中質粒蛋白的表達及流式細胞技術檢測細胞凋亡比例。
結果轉染pwtp53和pMDM2質粒的HepG2細胞均可見p53及MDM2蛋白條帶，同時轉染pSUMO-1質粒的細胞分別可見被SUMO-1修飾的相對分子量較大的p53和MDM2蛋白條帶，在未轉染任何質粒、僅轉染空質粒和pSUMO1質粒的細胞中只檢測到少量p53蛋白表達。轉染pwtp53及pwtp53+pSUMO-1質粒的HepG2細胞凋亡比例分別為(16.79±1.62)%和(18.15±1.36)%，轉染pwtp53+pMDM2+pSUMO-1質粒的細胞凋亡比例為(14.06±1.84)%，轉染pwtp53+pMDM2質粒的細胞凋亡比例則下降至(5.17±1.23)%，與前三者比較差異有顯著性意義(PH＜0.01)；其他轉染系細胞中的細胞凋亡比例均≤2%，差異無顯著性意義。
結論 SUMO-1通過與p53蛋白的結合或翻譯后修飾，抑制MDM2等癌基因蛋白對p53蛋白的降解，可增強p53抑癌基因誘導的細胞凋亡。

引用本文： 盧星榕,易繼林. SUMO-1對p53基因誘導HepG2細胞凋亡的增強作用. 中國普外基礎與臨床雜志, 2005, 12(4): 371-374. doi: 復制

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2.	Rosenfeld MR, Meneses P, Dalmau J, et al. Gene transfer of wildtype p53 results in restoration of tumorsuppressor function in a medulloblastoma cell line [Ｊ]. Neurology, 1995; 45(8)∶1533.
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4.	Haupt Y, Maya R, Kazaz A, et al. Mdm2 promotes the rapid degradation of p53 [Ｊ]. Nature, 1997; 387(6630)∶296.
5.	Saitoh H,Hinchey J. Functional heterogeneity of small ubiquitinrelated protein modifiers SUMO1 versus SUMO2/3 [Ｊ]. J Biol Chem, 2000; 275(9)∶6252.
6.	Bayer P, Arndt A, Metzger S, et al. Structure determination of the small ubiquitinrelated modifier SUMO1 [Ｊ]. J Mol Biol, 1998; 280(2)∶275.
7.	Muller S, Hoege C, Pyrowolakis G, et al. SUMO, ubiquitin’s mysterious cousin [Ｊ]. Nat Rev Mol Cell Biol, 2001; 2(3)∶202.
8.	Melchior F. SUMO——nonclassical ubiquitin [Ｊ]. Annu Rev Cell Dev Biol, 2000; 16∶591.
9.	Rodriguez MS, Desterro JM, Lain S, et al. SUMO1 modification activates the transcriptional response of p53 [Ｊ]. EMBO J, 1999; 18(22)∶6455.
10.	Gostissa M, Hengstermann A, Fogal V, et al. Activation of p53 by conjugation to the ubiquitinlike protein SUMO1 [Ｊ]. EMBO J, 1999; 18(22)∶6462.
11.	Sambrook J, Ftitsch EF, Mauitis T. Molecular cloning.A laboratory manual [M]. 2nd. New York: Cold Spring Harbor Laboratory Press, 1988∶362-371,792-793.
12.	Zheleva DI, Lane DP, Fischer PM. The p53Mdm2 pathway: targets for the development of new anticancer therapeutics [Ｊ]. Mini Rev Med Chem, 2003; 3(3)∶257.
13.	Kurepa J, Walker JM, Smalle J, et al. The small ubiquitinlike modifier (SUMO) protein modification system in Arabidopsis. Accumulation of SUMO1 and 2 conjugates is increased by stress [Ｊ]. J Biol Chem, 2003; 278(9)∶6862.

1. Ko LJ, Prives C. p53: puzzle and paradigm [Ｊ]. Genes Dev, 1996; 10(9)∶1054.
2. Rosenfeld MR, Meneses P, Dalmau J, et al. Gene transfer of wildtype p53 results in restoration of tumorsuppressor function in a medulloblastoma cell line [Ｊ]. Neurology, 1995; 45(8)∶1533.
3. Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53 [Ｊ]. FEBS Lett, 1997; 420(1)∶25.
4. Haupt Y, Maya R, Kazaz A, et al. Mdm2 promotes the rapid degradation of p53 [Ｊ]. Nature, 1997; 387(6630)∶296.
5. Saitoh H,Hinchey J. Functional heterogeneity of small ubiquitinrelated protein modifiers SUMO1 versus SUMO2/3 [Ｊ]. J Biol Chem, 2000; 275(9)∶6252.
6. Bayer P, Arndt A, Metzger S, et al. Structure determination of the small ubiquitinrelated modifier SUMO1 [Ｊ]. J Mol Biol, 1998; 280(2)∶275.
7. Muller S, Hoege C, Pyrowolakis G, et al. SUMO, ubiquitin’s mysterious cousin [Ｊ]. Nat Rev Mol Cell Biol, 2001; 2(3)∶202.
8. Melchior F. SUMO——nonclassical ubiquitin [Ｊ]. Annu Rev Cell Dev Biol, 2000; 16∶591.
9. Rodriguez MS, Desterro JM, Lain S, et al. SUMO1 modification activates the transcriptional response of p53 [Ｊ]. EMBO J, 1999; 18(22)∶6455.
10. Gostissa M, Hengstermann A, Fogal V, et al. Activation of p53 by conjugation to the ubiquitinlike protein SUMO1 [Ｊ]. EMBO J, 1999; 18(22)∶6462.
11. Sambrook J, Ftitsch EF, Mauitis T. Molecular cloning.A laboratory manual [M]. 2nd. New York: Cold Spring Harbor Laboratory Press, 1988∶362-371,792-793.
12. Zheleva DI, Lane DP, Fischer PM. The p53Mdm2 pathway: targets for the development of new anticancer therapeutics [Ｊ]. Mini Rev Med Chem, 2003; 3(3)∶257.
13. Kurepa J, Walker JM, Smalle J, et al. The small ubiquitinlike modifier (SUMO) protein modification system in Arabidopsis. Accumulation of SUMO1 and 2 conjugates is increased by stress [Ｊ]. J Biol Chem, 2003; 278(9)∶6862.

《中國普外基礎與臨床雜志》

SUMO-1對p53基因誘導HepG2細胞凋亡的增強作用

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《中國普外基礎與臨床雜志》

SUMO-1對p53基因誘導HepG2細胞凋亡的增強作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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