Browse > Article
http://dx.doi.org/10.4196/kjpp.2014.18.1.73

Bcl-2 Knockdown Accelerates T Cell Receptor-Triggered Activation-Induced Cell Death in Jurkat T Cells  

Lee, Yun-Jung (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Won, Tae Joon (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Hyung, Kyeong Eun (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Lee, Mi Ji (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Moon, Young-Hye (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Lee, Ik Hee (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Go, Byung Sung (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Hwang, Kwang Woo (Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.18, no.1, 2014 , pp. 73-78 More about this Journal
Abstract
Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-${\kappa}B$) translocation.
Keywords
AICD; Apoptosis; Bcl-2; shRNA; T cell;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Langenau DM, Jette C, Berghmans S, Palomero T, Kanki JP, Kutok JL, Look AT. Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish. Blood. 2005;105:3278-3285.   DOI   ScienceOn
2 Liao G, Zhang M, Harhaj EW, Sun SC. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptorassociated factor 3-induced degradation. J Biol Chem. 2004; 279:26243-26250.   DOI   ScienceOn
3 Fleckenstein DS, Dirks WG, Drexler HG, Quentmeier H. Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine kinase. Leuk Res. 2003;27:687-694.   DOI   ScienceOn
4 Gaumer S, Guénal I, Brun S, Théodore L, Mignotte B. Bcl-2 and Bax mammalian regulators of apoptosis are functional in Drosophila. Cell Death Differ. 2000;7:804-814.   DOI
5 Hengartner MO, Ellis RE, Horvitz HR. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature. 1992;356:494-499.   DOI   ScienceOn
6 Hengartner MO, Horvitz HR. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian protooncogene bcl-2. Cell. 1994;76:665-676.   DOI   ScienceOn
7 Nicolas O, Gavín R, Braun N, Ureña JM, Fontana X, Soriano E, Aguzzi A, del Río JA. Bcl-2 overexpression delays caspase-3 activation and rescues cerebellar degeneration in prion-deficient mice that overexpress amino-terminally truncated prion. FASEB J. 2007;21:3107-3117.   DOI   ScienceOn
8 Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6:99-104.   DOI   ScienceOn
9 Li Q, Ching AK, Chan BC, Chow SK, Lim PL, Ho TC, Ip WK, Wong CK, Lam CW, Lee KK, Chan JY, Chui YL. A death receptor-associated anti-apoptotic protein, BRE, inhibits mitochondrial apoptotic pathway. J Biol Chem. 2004;279: 52106-52116.   DOI   ScienceOn
10 Cui X, Hawari F, Alsaaty S, Lawrence M, Combs CA, Geng W, Rouhani FN, Miskinis D, Levine SJ. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. J Clin Invest. 2002;110:515-526.   DOI
11 Xu Y, Cheng G, Baltimore D. Targeted disruption of TRAF3 leads to postnatal lethality and defective T-dependent immune responses. Immunity. 1996;5:407-415.   DOI   ScienceOn
12 Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997;275:1129-1132.   DOI   ScienceOn
13 Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411-452.   DOI   ScienceOn
14 Laster SM, Wood JG, Gooding LR. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. J Immunol. 1988;141:2629-2634.
15 Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J. Human ICE/CED-3 protease nomenclature. Cell. 1996;87:171.   DOI   ScienceOn
16 Chinnaiyan AM, Orth K, O'Rourke K, Duan H, Poirier GG, Dixit VM. Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3-like apoptotic proteases. J Biol Chem. 1996;271:4573-4576.   DOI
17 Erhardt P, Cooper GM. Activation of the CPP32 apoptotic protease by distinct signaling pathways with differential sensitivity to Bcl-xL. J Biol Chem. 1996;271:17601-17604.   DOI   ScienceOn
18 Armstrong RC, Aja T, Xiang J, Gaur S, Krebs JF, Hoang K, Bai X, Korsmeyer SJ, Karanewsky DS, Fritz LC, Tomaselli KJ. Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors. J Biol Chem. 1996;271:16850-16855.   DOI   ScienceOn
19 Shimizu S, Eguchi Y, Kamiike W, Matsuda H, Tsujimoto Y. Bcl-2 expression prevents activation of the ICE protease cascade. Oncogene. 1996;12:2251-2257.
20 Vaux DL, Weissman IL, Kim SK. Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science. 1992;258:1955-1957.   DOI
21 Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281:1305-1308.   DOI   ScienceOn
22 Van Parijs L, Biuckians A, Abbas AK. Functional roles of Fas and Bcl-2-regulated apoptosis of T lymphocytes. J Immunol. 1998;160:2065-2071.
23 Russell JH, Wang R. Autoimmune gld mutation uncouples suicide and cytokine/proliferation pathways in activated, mature T cells. Eur J Immunol. 1993;23:2379-2382.   DOI   ScienceOn
24 Rieux-Laucat F, Le Deist F, Fischer A. Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathways. Cell Death Differ. 2003;10:124-133.   DOI   ScienceOn
25 Igney FH, Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002;2:277-288.   DOI   ScienceOn
26 Schmitz I, Kirchhoff S, Krammer PH. Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol. 2000;32:1123-1136.   DOI   ScienceOn
27 Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991;66:233-243.   DOI   ScienceOn
28 Trauth BC, Klas C, Peters AM, Matzku S, Möller P, Falk W, Debatin KM, Krammer PH. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989; 245:301-305.   DOI
29 Fraser A, Evan G. A license to kill. Cell. 1996;85:781-784.   DOI   ScienceOn
30 Russell JH, Rush B, Weaver C, Wang R. Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide. Proc Natl Acad Sci U S A. 1993;90:4409-4413.   DOI
31 Bossu P, Singer GG, Andres P, Ettinger R, Marshak-Rothstein A, Abbas AK. Mature CD4+ T lymphocytes from MRL/lpr mice are resistant to receptor-mediated tolerance and apoptosis. J Immunol. 1993;151:7233-7239.
32 Alderson MR, Tough TW, Davis-Smith T, Braddy S, Falk B, Schooley KA, Goodwin RG, Smith CA, Ramsdell F, Lynch DH. Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med. 1995;181:71-77.   DOI   ScienceOn
33 Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol. 2001;11:372-377.   DOI   ScienceOn
34 Paul NL, Ruddle NH. Lymphotoxin. Annu Rev Immunol. 1988;6:407-438.   DOI   ScienceOn
35 Beutler B, Cerami A. Tumor necrosis, cachexia, shock, and inflammation: a common mediator. Annu Rev Biochem. 1988; 57:505-518.   DOI   ScienceOn
36 Beutler B, Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625-655.   DOI   ScienceOn