RTKN2 Induces NF-KappaB Dependent Resistance to Intrinsic Apoptosis in HEK Cells and Regulates BCL-2 Genes in Human CD4+ Lymphocytes:

作者: Fiona M Collier , Andrea Loving , Adele J Baker , Janet McLeod , Ken Walder

DOI: 10.4137/JCD.S2891

关键词:

摘要: The gene for Rhotekin 2 (RTKN2) was originally identified in a promyelocytic cell line resistant to oxysterol-induced apoptosis. It is differentially expressed freshly isolated CD4+ T-cells compared with other hematopoietic cells and down-regulated following activation of the T-cell receptor. However, very little known about function RTKN2 than its homology Rho-GTPase effector, rhotekin, possibility that they may have similar roles. Here we show stable expression HEK enhanced survival response intrinsic apoptotic agents; 25-hydroxy cholesterol camptothecin, but not extrinsic agent, TNFα. Inhibitors NF-KappaB, MAPK, reversed resistance mitochondrial pro-apoptotic genes, Bax Bim, were down regulated. In these cells, there no evidence binding GTPases, RhoA or Rac2. Consistent role over-expressing suppression primary human reduced viability increased sensitivity 25-OHC. Bim while BCL-2 decreased. both models played process apoptosis this dependent on either NF-KappaB signaling downstream genes. As highly it play as key switch regulation genes involved survival.

参考文章(45)
Peter T Daniel, Klaus Schulze-Osthoff, Claus Belka, Dilek Güner, Guardians of cell death: the Bcl-2 family proteins Essays in Biochemistry. ,vol. 39, pp. 73- 88 ,(2003) , 10.1042/BSE0390073
Pramod C. Rath, Bharat B. Aggarwal, TNF-induced signaling in apoptosis. Journal of Clinical Immunology. ,vol. 19, pp. 350- 364 ,(1999) , 10.1023/A:1020546615229
Jian Zhang, Katalin Mikecz, Alison Finnegan, Tibor T. Glant, Spontaneous Thymocyte Apoptosis Is Regulated by a Mitochondrion-Mediated Signaling Pathway Journal of Immunology. ,vol. 165, pp. 2970- 2974 ,(2000) , 10.4049/JIMMUNOL.165.6.2970
Yan Shou, Nianyu Li, Li Li, Joseph L. Borowitz, Gary E. Isom, NF‐κB‐mediated up‐regulation of Bcl‐XS and Bax contributes to cytochrome c release in cyanide‐induced apoptosis Journal of Neurochemistry. ,vol. 81, pp. 842- 852 ,(2002) , 10.1046/J.1471-4159.2002.00880.X
Elisabetta Vegeto, Giuseppe Pollio, Carlo Pellicciari, Adriana Maggi, Estrogen and progesterone induction of survival of monoblastoid cells undergoing TNF-α-induced apoptosis The FASEB Journal. ,vol. 13, pp. 793- 803 ,(1999) , 10.1096/FASEBJ.13.8.793
Upasna Gaur, Bharat B. Aggarwal, Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochemical Pharmacology. ,vol. 66, pp. 1403- 1408 ,(2003) , 10.1016/S0006-2952(03)00490-8
Hans-Ingo Trompeter, Sandra Weinhold, Corinna Thiel, Peter Wernet, Markus Uhrberg, Rapid and highly efficient gene transfer into natural killer cells by nucleofection. Journal of Immunological Methods. ,vol. 274, pp. 245- 256 ,(2003) , 10.1016/S0022-1759(02)00431-3
Hannes Hentze, Markus Latta, Gerald Künstle, Saravanakumar Dhakshinamoorthy, Poh Yong Ng, Alan G. Porter, Albrecht Wendel, Topoisomerase inhibitor camptothecin sensitizes mouse hepatocytes in vitro and in vivo to TNF‐mediated apoptosis Hepatology. ,vol. 39, pp. 1311- 1320 ,(2004) , 10.1002/HEP.20174
Wendy Lai, Cheong-Hee Chang, Donna L. Farber, Gene transfection and expression in resting and activated murine CD4 T cell subsets Journal of Immunological Methods. ,vol. 282, pp. 93- 102 ,(2003) , 10.1016/J.JIM.2003.07.015
P. A. Alexander, Y. He, Y. Chen, J. Orban, P. N. Bryan, The design and characterization of two proteins with 88% sequence identity but different structure and function Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 11963- 11968 ,(2007) , 10.1073/PNAS.0700922104