The Role of Bcl-x(L) Protein in Nucleotide Excision Repair–Facilitated Cell Protection Against Cisplatin-Induced Apoptosis

作者: Stephanie L. Lomonaco , Xiaoxin S. Xu , Gan Wang

DOI: 10.1089/DNA.2008.0815

关键词:

摘要: Many anticancer drugs target the genomic DNA of cancer cells by generating damage and inducing apoptosis. repair protects against damage–induced Although mechanisms apoptosis have been extensively studied, mechanism which prevents is not fully understood. We studied role antiapoptotic Bcl-x(L) protein in nucleotide excision (NER)–facilitated cell protection cisplatin-induced Using both normal human fibroblasts (NF) NER-defective xeroderma pigmentosum group A (XPA) G (XPG) fibroblasts, we demonstrated that a functional NER required for transcription bcl-x(l) gene. The results obtained from our Western blots revealed cisplatin treatment led to an increase level NF cells, but decrease XPA XPG cells. immunofluorescence staining indicated pathway was translocation NF-κB p65 cytoplasm into nucleus, indicative activation. Given important function regulating gene preventing apoptosis, these suggest may protect activating NF-κB, further induces gene, resulting accumulation activation survival leads increased under treatment.

参考文章(61)
J. Bae, S. Y. Hsu, C. P. Leo, K. Zell, A. J. W. Hsueh, Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis. Apoptosis. ,vol. 6, pp. 319- 330 ,(2001) , 10.1023/A:1011319901057
Jerry E Chipuk, Tomomi Kuwana, Lisa Bouchier-Hayes, Nathalie M Droin, Donald D Newmeyer, Martin Schuler, Douglas R Green, None, Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. ,vol. 303, pp. 1010- 1014 ,(2004) , 10.1126/SCIENCE.1092734
Ana Janićijević, Kaoru Sugasawa, Yuichiro Shimizu, Fumio Hanaoka, Nils Wijgers, Miodrag Djurica, Jan HJ Hoeijmakers, Claire Wyman, DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair. ,vol. 2, pp. 325- 336 ,(2003) , 10.1016/S1568-7864(02)00222-7
S Zinkel, A Gross, E Yang, BCL2 family in DNA damage and cell cycle control. Cell Death & Differentiation. ,vol. 13, pp. 1351- 1359 ,(2006) , 10.1038/SJ.CDD.4401987
Pithi Chanvorachote, Ubonthip Nimmannit, Christian Stehlik, Liying Wang, Bing-Hua Jiang, Boonsri Ongpipatanakul, Yon Rojanasakul, Nitric Oxide Regulates Cell Sensitivity to Cisplatin-Induced Apoptosis through S-Nitrosylation and Inhibition of Bcl-2 Ubiquitination Cancer Research. ,vol. 66, pp. 6353- 6360 ,(2006) , 10.1158/0008-5472.CAN-05-4533
Stephanie L. Colton, Xiaoxin S. Xu, Y. Alan Wang, Gan Wang, The involvement of ataxia-telangiectasia mutated protein activation in nucleotide excision repair-facilitated cell survival with cisplatin treatment. Journal of Biological Chemistry. ,vol. 281, pp. 27117- 27125 ,(2006) , 10.1074/JBC.M602826200
John R. Jeffers, Evan Parganas, Youngsoo Lee, Chunying Yang, JinLing Wang, Jennifer Brennan, Kirsteen H. MacLean, Jiawen Han, Thomas Chittenden, James N. Ihle, Peter J. McKinnon, John L. Cleveland, Gerard P. Zambetti, Puma is an essential mediator of p53-dependent and -independent apoptotic pathways Cancer Cell. ,vol. 4, pp. 321- 328 ,(2003) , 10.1016/S1535-6108(03)00244-7
Philip C Hanawalt, Subpathways of nucleotide excision repair and their regulation. Oncogene. ,vol. 21, pp. 8949- 8956 ,(2002) , 10.1038/SJ.ONC.1206096