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Human TIEG2/KLF11 induces oligodendroglial cell death by downregulation of Bcl-XL expression

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Summary

TGF-β-induced apoptosis is essential for embryonic development and mainteanance of adult tissues. Impairment of the apoptotic pathway, regulated by TGF-β, plays a center role in tumorigenesis and manifestations of different diseases. TIEG2/KLF11 is a recently identified human TGF-β-inducible zinc finger protein belonging to the family of Sp1/KLF-like transcription factors. In human and murine tissues it has been shown that TIEG1 and TIEG2 induce apoptosis and inhibit cell growth. Since TGF-β and Tieg1 are able to induce apoptosis in the oligodendroglial cell line OLI-neu, we analysed the ability of TIEG2 to mimic the effects observed after treatment with TGF-β and overexpression of Tieg1. Herein we report that TIEG2 induces Caspase3-dependent apoptosis in murine OLI-neu cells. Furthermore, we could demonstrate that TIEG2 decreases the levels of the anti-apoptotic protein Bcl-XL and inhibits transcription driven by the Bcl-XL promoter. These data suggest that TIEG2 serves as a downstream mediator of TGF-β, bridging TGF-β-dependent signaling to the intracellular pathway of apoptosis.

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References

  • H Bender Z Wang N Schuster K Krieglstein (2004) ArticleTitleTIEG1 facilitates transforming growth factor-β-mediated apoptosis in the oligodendroglial cell line OLI-neu J Neurosci Res 75 344–352 Occurrence Handle14743447 Occurrence Handle10.1002/jnr.10856 Occurrence Handle1:CAS:528:DC%2BD2cXhtlGku7w%3D

    Article  PubMed  CAS  Google Scholar 

  • CL Buenemann C Willy A Buchmann A Schmiechen M Schwarz (2001) ArticleTitleTransforming growth factor-beta1-induced Smad signalling, cell-cycle arrest and apoptosis in hepatoma cells Carcinogenesis 22 447–452 Occurrence Handle11238185 Occurrence Handle10.1093/carcin/22.3.447 Occurrence Handle1:CAS:528:DC%2BD3MXitFKhtr4%3D

    Article  PubMed  CAS  Google Scholar 

  • E Chalaux T López-Rovira JL Rosa G Pons LM Boxer R Bartrons F Ventura (1999) ArticleTitleA zinc-finger transcription factor induced by TGF-β promotes apoptotic cell death in epithelial Mv1Lu cells FEBS Lett 457 478–482 Occurrence Handle10471833 Occurrence Handle10.1016/S0014-5793(99)01051-0 Occurrence Handle1:CAS:528:DyaK1MXls12hsLc%3D

    Article  PubMed  CAS  Google Scholar 

  • JE Chipuk M Bhat AY Hsing J Ma D Danielpour (2001) ArticleTitleBcl-XL blocks transforming growth factor-beta1-induced apoptosis by inhibiting cytochrome c release and not by directly antogonizing Apaf-1-dependent caspase activation in prostate epithelial cells J Biol Chem 276 26614–26621 Occurrence Handle11320089 Occurrence Handle10.1074/jbc.M100913200 Occurrence Handle1:CAS:528:DC%2BD3MXlsVKntb0%3D

    Article  PubMed  CAS  Google Scholar 

  • T Cook R Urrutia (2000) ArticleTitleTIEG proteins join the Smads as TGF-beta-regulated transcription factors that control pancreatic cell growth Am J Physiol Gastrointest Liver Physiol 278 513–521

    Google Scholar 

  • T Cook B Gebelein K Mesa A Mladek R Urrutia (1998) ArticleTitleMolecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth J Biol Chem 273 25929–25936 Occurrence Handle9748269 Occurrence Handle10.1074/jbc.273.40.25929 Occurrence Handle1:CAS:528:DyaK1cXms1egtL4%3D

    Article  PubMed  CAS  Google Scholar 

  • T Cook B Gebelein M Belal K Mesa R Urrutia (1999) ArticleTitleThree conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins J Biol Chem 274 29500–29504 Occurrence Handle10506214 Occurrence Handle10.1074/jbc.274.41.29500 Occurrence Handle1:CAS:528:DyaK1MXmslajsrw%3D

    Article  PubMed  CAS  Google Scholar 

  • R Derynck YE Zhang (2003) ArticleTitleSmad-dependent and Smad-independent pathways in TGF-beta family signalling Nature 425 577–584 Occurrence Handle14534577 Occurrence Handle10.1038/nature02006 Occurrence Handle1:CAS:528:DC%2BD3sXnvV2hs7c%3D

    Article  PubMed  CAS  Google Scholar 

  • R Derynck RJ Akhurst A Balmain (2001) ArticleTitleTGF-beta signaling in tumor suppression and cancer progression Nat Genet 29 117–129 Occurrence Handle11586292 Occurrence Handle10.1038/ng1001-117 Occurrence Handle1:CAS:528:DC%2BD3MXnsFKgt7c%3D

    Article  PubMed  CAS  Google Scholar 

  • N Dünker N Schuster K Krieglstein (2001) ArticleTitleTGF-β modulates programmed cell death in the retina of the developing chick embryo Development 128 1933–1942 Occurrence Handle11493517

    PubMed  Google Scholar 

  • N Dünker K Schmitt K Krieglstein (2002a) ArticleTitleTGF-beta is required for programmed cell death in interdigital webs of the developing mouse limb Mech Dev 113 111–120 Occurrence Handle10.1016/S0925-4773(02)00015-1

    Article  Google Scholar 

  • N Dünker K Schmitt N Schuster K Krieglstein (2002b) ArticleTitleThe role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa Gastroenterology 122 1364–1375 Occurrence Handle10.1053/gast.2002.32991

    Article  Google Scholar 

  • MP Fautsch A Vrabel D Rickard M Subramaniam TC Spelsberg ED Wieben (1998) ArticleTitleCharacterization of the mouse TGFβ-inducible early gene (TIEG): conservation of exon and transscriptional regulatory sequences with evidence of additional transcripts Mamm Genome 9 838–842 Occurrence Handle9745041 Occurrence Handle10.1007/s003359900878 Occurrence Handle1:CAS:528:DyaK1cXmsVehsr0%3D

    Article  PubMed  CAS  Google Scholar 

  • ME Fernandez-Zapico A Mladek V Ellenrieder E Folch-Puy L Miller R Urrutia (2003) ArticleTitleAn mSin3A interaction domain links the transcriptional activity of KLF11 with its role in growth regulation EMBO J 22 4748–4758 Occurrence Handle12970187 Occurrence Handle10.1093/emboj/cdg470 Occurrence Handle1:CAS:528:DC%2BD3sXnt1Kjtr0%3D

    Article  PubMed  CAS  Google Scholar 

  • DA Grillot M Gonzalez-Garcia D Ekhterae L Duan N Inohara S Ohta MF Seldin G Nunez (1997) ArticleTitleGenomic organization, promoter region analysis, and chromosome localization of the mouse bcl-x gene J Immunol 158 4750–4757 Occurrence Handle9144489 Occurrence Handle1:CAS:528:DyaK2sXjtFKjs78%3D

    PubMed  CAS  Google Scholar 

  • A Gross JM McDonnell SJ Korsmeyer (1999) ArticleTitleBCL-2 family members and the mitochondria in apoptosis Genes Dev 13 1899–1911 Occurrence Handle10444588 Occurrence Handle1:CAS:528:DyaK1MXltlGktrg%3D

    PubMed  CAS  Google Scholar 

  • TE Hefferan M Subramaniam S Khosla BL Riggs TC Spelsberg (2000) ArticleTitleCytokine-specific induction of the TGF-β inducible early gene (TIEG): regulation by specific members of the TGF-β family J Cell Biochem 78 380–390 Occurrence Handle10861837 Occurrence Handle10.1002/1097-4644(20000901)78:3<380::AID-JCB4>3.0.CO;2-L Occurrence Handle1:CAS:528:DC%2BD3cXltlSht7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • MD Jacobson M Weil MC Raff (1997) ArticleTitleProgrammed cell death in animal development Cell 88 347–354 Occurrence Handle9039261 Occurrence Handle10.1016/S0092-8674(00)81873-5 Occurrence Handle1:CAS:528:DyaK2sXhtFahtbw%3D

    Article  PubMed  CAS  Google Scholar 

  • K Krieglstein S Richter L Farkas N Schuster N Dünker RW Oppenheim K Unsicker (2000) ArticleTitleReduction of endogenous transforming growth factor β prevents ontogenetic neuron death Nat Neurosci 3 1085–1090 Occurrence Handle11036264 Occurrence Handle10.1038/80598 Occurrence Handle1:STN:280:DC%2BD3M%2Flt1eiuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • J Massague (1998) ArticleTitleTGF-beta signal transduction Annu Rev Biochem 67 753–791 Occurrence Handle9759503 Occurrence Handle10.1146/annurev.biochem.67.1.753 Occurrence Handle1:CAS:528:DyaK1cXlsFOmsbY%3D

    Article  PubMed  CAS  Google Scholar 

  • J Massague D Wotton (2000) ArticleTitleTranscriptional control by the TGF-beta/Smad signaling system EMBO J 19 1745–1754 Occurrence Handle10775259 Occurrence Handle10.1093/emboj/19.8.1745 Occurrence Handle1:CAS:528:DC%2BD3cXivVKlsbo%3D

    Article  PubMed  CAS  Google Scholar 

  • N Motoyama F Wang KA Roth H Sawa K Nakayama I Negishi S Senju Q Zhang S Fujii (1995) ArticleTitleMassive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice Science 267 1506–1510 Occurrence Handle7878471 Occurrence Handle10.1126/science.7878471 Occurrence Handle1:CAS:528:DyaK2MXktlCltLk%3D

    Article  PubMed  CAS  Google Scholar 

  • ZN Oltvai CL Milliman SJ Korsmeyer (1993) ArticleTitleBcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death Cell 74 609–619 Occurrence Handle8358790 Occurrence Handle10.1016/0092-8674(93)90509-O Occurrence Handle1:CAS:528:DyaK3sXms1eqtbs%3D

    Article  PubMed  CAS  Google Scholar 

  • A Ribeiro SF Bronk PJ Roberts R Urrutia GJ Gores (1999) ArticleTitleThe transforming growth factor beta(1)-inducible transcription factor TIEG1, mediates apoptosis through oxidative stress Hepatology 30 1490–1497 Occurrence Handle10573529 Occurrence Handle10.1002/hep.510300620 Occurrence Handle1:CAS:528:DC%2BD3cXktVWq

    Article  PubMed  CAS  Google Scholar 

  • N Schuster K Krieglstein (2002) ArticleTitleMechanisms of TGF-β-mediated apoptosis Cell Tissue Res 307 1–14 Occurrence Handle11810309 Occurrence Handle10.1007/s00441-001-0479-6 Occurrence Handle1:CAS:528:DC%2BD3MXovFSgsLs%3D

    Article  PubMed  CAS  Google Scholar 

  • N Schuster H Bender A Philippi S Subramaniam J Strelau Z Wang K Krieglstein (2002) ArticleTitleTGF-β induces cell death in the oligodendroglial cell line OLI-neu GLIA 40 95–108 Occurrence Handle12237847 Occurrence Handle10.1002/glia.10110

    Article  PubMed  Google Scholar 

  • M Seto U Jaeger RD Hockett W Graninger S Bennett P Goldman ST Korsmeyer (1988) ArticleTitleAlternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma EMBO J 7 123–131 Occurrence Handle2834197 Occurrence Handle1:CAS:528:DyaL1cXhtVOgtrc%3D

    PubMed  CAS  Google Scholar 

  • CZ Song G Gavriilidis H Asano G Stamatoyannopoulos (2005) ArticleTitleFunctional study of transcription factor KLF11 by targeted gene inactivation Blood Cells Mol Dis 34 53–59 Occurrence Handle15607700 Occurrence Handle10.1016/j.bcmd.2004.08.027 Occurrence Handle1:CAS:528:DC%2BD2cXhtVykurvP

    Article  PubMed  CAS  Google Scholar 

  • M Subramaniam SA Harris MJ Oursler K Rasmussen BL Riggs TC Spelsberg (1995) ArticleTitleIdentification of a novel TGF-beta-regulated gene encoding a putative zinc finger protein in human osteoblasts Nucleic Acids Res 23 4907–4912 Occurrence Handle8532536 Occurrence Handle10.1093/nar/23.23.4907 Occurrence Handle1:CAS:528:DyaK28XjsF2ktQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Subramaniam G Gorny SA Johnsen DG Monroe GL Evans DG Fraser DJ Rickard K Rasmussen JM van Deursen RT Turner MJ Oursler TC Spelsberg (2005) ArticleTitleTIEG1 null mouse-derived osteoblasts are defective in mineralization and in support of osteoclast differentiation in vitro Mol Cell Biol 25 1191–1199 Occurrence Handle15657444 Occurrence Handle10.1128/MCB.25.3.1191-1199.2005 Occurrence Handle1:CAS:528:DC%2BD2MXptF2jsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • I Tachibana M Imoto PN Adjei GJ Gores M Subramaniam TC Speksberg R Urrutia (1997) ArticleTitleOverexpression of the TGFβ-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells J Clin Invest 99 2365–2374 Occurrence Handle9153278 Occurrence Handle1:CAS:528:DyaK2sXjsVGqsbY%3D Occurrence Handle10.1172/JCI119418

    Article  PubMed  CAS  Google Scholar 

  • KR Tau TE Hefferan KM Waters JA Robinson M Subramaniam BL Riggs TC Spelsberg (1998) ArticleTitleEstrogen regulation of a transforming growth factor-β inducible early gene that inhibits deoxyribonucleic acid synthesis in human osteoblasts Endocrinology 139 1346–1353 Occurrence Handle9492071 Occurrence Handle10.1210/en.139.3.1346 Occurrence Handle1:CAS:528:DyaK1cXhtlejurc%3D

    Article  PubMed  CAS  Google Scholar 

  • NA Wahab BS Weston RM Mason (2005) ArticleTitleModulation of the TGFβ/Smad signaling pathway in mesangial cells by CTGF/CCN2 Exp Cell Res 307 305–314 Occurrence Handle15950619 Occurrence Handle10.1016/j.yexcr.2005.03.022 Occurrence Handle1:CAS:528:DC%2BD2MXltFSqtr4%3D

    Article  PubMed  CAS  Google Scholar 

  • Z Wang B Peters S Klussmann H Bender A Herb K Krieglstein (2004) ArticleTitleGene structure and evolution of Tieg3, a new member of the Tieg family of proteins Gene 325 25–34 Occurrence Handle14697507 Occurrence Handle10.1016/j.gene.2003.09.045 Occurrence Handle1:CAS:528:DC%2BD3sXpvFequro%3D

    Article  PubMed  CAS  Google Scholar 

  • S Yajima CH Lammers SH Lee Y Hara K Mizuno MM Mouradian (1997) ArticleTitleCloning and characterization of murine glial cell-derived neurotrophic factor inducible transcription factor (MGIF) J Neurosci 17 8657–8666 Occurrence Handle9348334 Occurrence Handle1:CAS:528:DyaK2sXnsFalsb4%3D

    PubMed  CAS  Google Scholar 

  • JS Zhang MC Monocrieffe J Kaczynski V Ellenrieder FG Prendergast R Urrutia (2001) ArticleTitleA conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A Mol Cell Biol 21 5041–5049 Occurrence Handle11438660 Occurrence Handle10.1128/MCB.21.15.5041-5049.2001 Occurrence Handle1:CAS:528:DC%2BD3MXlsVGitL8%3D

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Center of Anatomy, Department of Neuroanatomy, University of Goettingen, Goettingen, Germany

    Z. Wang, B. Spittau, M. Behrendt & K. Krieglstein

  2. Department of Anatomy, University of Saarland, Homburg, Germany

    B. Peters

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  1. Z. Wang
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  2. B. Spittau
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  3. M. Behrendt
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  4. B. Peters
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  5. K. Krieglstein
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First two authors contributed equally to this work

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Wang, Z., Spittau, B., Behrendt, M. et al. Human TIEG2/KLF11 induces oligodendroglial cell death by downregulation of Bcl-XL expression. J Neural Transm 114, 867–875 (2007). https://doi.org/10.1007/s00702-007-0635-6

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  • DOI: https://doi.org/10.1007/s00702-007-0635-6

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