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Ionizing radiation and TNF-a stimulate gene expression of a Thr/Tyr -protein phosphatase HVH1 and inhibitory factor IkBa in human squamous carcinoma cells

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Abstract

Exposure of cells to ionizing radiation (IR) or tumor necrosis factor-a(TNF-a) results in the stimulation of the DNA binding activities oftranscription factors, AP-1 and NF-kB. HVH1/CL100, a dual specificityprotein phosphatase, may attenuate the AP-1 response by dephosphorylating akey upstream element, mitogen-activated protein kinase (MAPK). The membersof IkB family of proteins regulate the NF-kB response. We examined theeffects of IR and TNF-a on HVH1 and IkBa gene expression. Our datademonstrate that IR or TNF-a treatment of head and neck squamous carcinomacells (PCI-04A) increased the steady-state levels of HVH1 and IkBa mRNAs;however, the induction patterns were different. TNF-a treatment led to arelatively prolonged stimulation of HVH1 and IkBa mRNAs lasting at least 7h, while IR caused a transient stimulation of these mRNAs and the expressionreturned to basal levels within 6 h post-IR treatment. Treatment of cellswith cycloheximide did not prevent the IR or TNF-a-inducible expression ofHVH1 and IkBa genes, indicating that these responses were independent of thenew protein synthesis. These data imply that protein phosphatase HVH1 andregulatory factor IkBa may play important roles in cellular response to IRand TNF-a. In addition, the kinetics of responsiveness indicates that themechanisms of IR and TNF-a-induced signalling are distinct.

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References

  1. Angel P, Karin M: The role of Jun, Fos, and the AP-1 complex in cell proliferation and transformation. Biochim Biophys Acta 1072: 129–157, 1991

    Google Scholar 

  2. Fornace AJ: Mammalian genes induced by radiation; Activation of genes associated with growth control. Annu Rev Genet 26: 507–526, 1992

    Google Scholar 

  3. Uckun FM, Schieven GL, Tuel-Ahlgren LM, Dibirdik I, Myers DE, Ledbetter JA, Song CW: Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors. Proc Natl Acad Sci USA 90: 252–256, 1993

    Google Scholar 

  4. Kharbanda S, Saleem A, Sharman T, Emoto Y, Weichselbaum RR, Kufe D: Activation of the pp90rsk and mitogen-activated serine/threonine protein kinases by ionizing radiation. Proc Natl Acad Sci 91: 5416–5420, 1994

    Google Scholar 

  5. Kasid U, Suy S, Dent P, Ray S, Whiteside TL, Sturgill TW: Activation of Raf by ionizing radiation. Nature 382: 813–816, 1996

    Google Scholar 

  6. Suy S, Anderson WB, Dent P, Chang E, Kasid U: Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast cancer cells. Oncogene (in press), 1997

  7. Hallahan DE, Guis D, Kuchibhotla J, Sukhatme V, Kufe DW, Weichselbaum RR: Radiation signalling mediated by Jun activation following dissociation from a cell type specific repressor. J Biol Chem 268: 4903–4907, 1993

    Google Scholar 

  8. Brach MA, Hass R, Sherman ML, Gunji H, Weichselbaum RR, Kufe D: Ionizing radiation induces expression and binding activity of the nuclear factor ?B. J Clin Invest 88: 691–695, 1991

    Google Scholar 

  9. Meighan-Mantha R, Riegel AT, Wang F-H, Whiteside TL, Kasid U: Gamma radiation stimulates octomer binding protein activity. Manuscript submitted

  10. Sahijdak WM, Yang C-R, Zuckerman JS, Meyers M, Boothman DA: Alterations in transcription factor binding in radioresistant human melanoma cells after ionizing radiation. Rad Res 138: S47–S51, 1994

    Google Scholar 

  11. Vassalli P: The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10: 411–452, 1992

    Google Scholar 

  12. Vandenabeele P, Declercg W, Beyaert R, Fiers W: Two tumour necrosis factor receptors: Structure and function. Trends Cell Biol 5: 392–399, 1995

    Google Scholar 

  13. Brenner DA, O'Hara M, Angel P, Chojkier M, Karin M: Prolonged activation of jun and collagenase genes by tumor necrosis factor-alpha. Nature 337: 661–663, 1989

    Google Scholar 

  14. Osborn L, Kunkel S, Nabel GJ: Tumor necrosis factor ??and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor ?B. Proc Natl Acad Sci USA 86: 2336–2340, 1989

    Google Scholar 

  15. Wang C-Y, Mayo MW, Baldwin AS: TNF-and cancer therapy-induced apoptosis: Potentiation by inhibition of NF-?B. Science 274: 784–787, 1996

    Google Scholar 

  16. Marshall CJ: Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation. Cell 80: 179–185, 1995

    Google Scholar 

  17. Cobb M, Goldsmith EJ: How MAP kinases are regulated? J Biol Chem 270: 14843–14846, 1995

    Google Scholar 

  18. Karin M: The regulation of AP-1 activity by mitogen-activated protein kineses. J Biol Chem 270: 16483–16486, 1995

    Google Scholar 

  19. Kharbanda S, Saleem A, Shafman T, Emoto Y, Weichselbaum RR, Woodgett J, Avruch J, Kyriakis J, Kufe D: Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev 9: 1586–1597, 1995

    Google Scholar 

  20. Kyriakis JM, Banerjee P, Nikoiakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J, Woodgett JR: The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369: 156–160, 1994

    Google Scholar 

  21. Derijard B, Hibi M, Wu I-H, Barrett T, Su B, Karin M, Davis R: JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76: 1025–1037, 1994

    Google Scholar 

  22. Liu Z-G, Hsu H, Goeddel D, Karin M: Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-?B activation prevents cell death. Cell 87: 565–576, 1996

    Google Scholar 

  23. Zheng C-F, Guan K-L: Dephosphorylation and inactivation of the mitogen-activated protein kinase by a mitogen-induced thr/tyr protein phosphatase. J Biol Chem 268: 16116–16119, 1993

    Google Scholar 

  24. Alessi DR, Smythe C, Keyse SM: The human CL100 gene encodes a tyr/thr-protein phosphatase which potently and specifically inactivates MAP kinase and suppresses its activation by oncogenic ras in Xenopusoocyte extracts. Oncogene 8: 2015–2020, 1993

    Google Scholar 

  25. Sun H, Tonks NK, Bar-Sagi D: Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1. Science 266: 285–288, 1994

    Google Scholar 

  26. Liu Y, Gorospe M, Yang C, Holbrook NJ: Role of mitogen-activated protein kinase phosphatase during the cellular response to genotoxic stress. J Biol Chem 270: 8377–8380, 1995

    Google Scholar 

  27. Keyes SM: An emerging family of dual specificity MAP kinase phosphatases. Biochim Biophys Acta 1265(2-3): 152–160, 1995

    Google Scholar 

  28. Keyse SM, Emslie EA: Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase. Nature 359: 644–647, 1992

    Google Scholar 

  29. Ishibashi T, Bottaro DP, Michieli P, Kelley CA, Aaronson SA: A novel dual specificity phosphatase induced by serum stimulation and heat shock. J Biol Chem 269: 29897–29902, 1994

    Google Scholar 

  30. Sun H, Charles CH, Lau LF, Tonks NK: MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell 75: 487–498, 1993

    Google Scholar 

  31. Baeuerle PA, Baltimore D: IkB: a specific inhibitor of the NF-?B transcription factor. Science 242: 540–546, 1988

    Google Scholar 

  32. Beg AA, Baldwin AS: The IkB proteins: multifunctional regulators of Rel/NF-?B transcription factors. Genes Dev 7: 2064–2070, 1993

    Google Scholar 

  33. Hay RT: Control of nuclear factor-?B DNA binding activity by inhibitor proteins containing ankyrin repeats. Biochem Soc Trans 21: 926–930, 1993

    Google Scholar 

  34. Brown K, Park S, Kanno T, Franzoso G, and Siebenlist U: Mutual regulation of the transcriptional activator NF-?B and its inhibitor, I?B?. Proc Natl Acad Sci USA 90: 2532–2536, 1993

    Google Scholar 

  35. Chen Z, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D, Maniatis T: Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev 9: 1586–1597, 1995

    Google Scholar 

  36. Heo DS, Synderman C, Gollin SM, Pan S, Walker E, Deka R, Barnes EI, Johnson JT, Herberman RB, Whiteside TL: Biology, cytogenetics, and sensitivity to immunological effector cells of new head and neck squamous cell carcinoma lines. Cancer Res 49: 5167–5175, 1989

    Google Scholar 

  37. Maniatis T, Fritsch EF, Aambrook J: Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, CSH Laboratory Press, 1982

    Google Scholar 

  38. Hall EJ: In: EJ Hall (ed). Radiobiology for the Radiologist. Lippincott, Philadelphia, 1988, pp 128–135

    Google Scholar 

  39. Yamauchi N, Kuriyama H, Watanabe N, Neda H, Maeda M, Niitsu Y: Intracellular hydroxy radical production induced by recombinant human tumor necrosis factor and its implications in the killing of tumor cells in vitro. Cancer Res 49: 1671–1675, 1989

    Google Scholar 

  40. Sacchi M, Klapan I, Johnson JT, Whiteside TLW: Antiproliferative effects of cytokines on squamous cell carcinoma. Archives of Otolaryngology-Head and Neck Surgery 117: 321–326, 1991

    Google Scholar 

  41. Kwak SP, Hakes DJ, Martell KJ, Dixon JE: Isolation and characterization of a human dual specificity protein-tyrosine phosphatase gene. J Biol Chem 269: 3596–3604, 1994

    Google Scholar 

  42. Le Bail O, Schmidt-Ullrich R, Isarel A: Promoter analysis of the gene encoding the I?B-?/MAD3 inhibitor of NF-?B: positive regulation by the members of the rel/NF-KB family. EMBO J 12: 5043–5049, 1993

    Google Scholar 

  43. Hallahan DE, Dunphy E, Virudachalam S, Sukhatme VP, Kufe DW, Weichselbaum RR: c-junand Egr-1 participate in DNA synthesis and cell survival in response to ionizing radiation exposure. J Biol Chem 270: 30303–30309, 1995

    Google Scholar 

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Authors and Affiliations

  1. Departments of Radiation Medicine, Lombardi Cancer Center, Georgetown University, Washington DC, 20007

    Usha Kasid & Fun-Han Wang

  2. Biochemistry and Molecular Biology, Lombardi Cancer Center, Georgetown University, Washington DC, 20007

    Usha Kasid

  3. Department of Pathology, Pittsburgh Cancer Institute, University of Pittsburgh, PA, 15213, USA

    Theresa L. Whiteside

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  1. Usha Kasid
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  2. Fun-Han Wang
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  3. Theresa L. Whiteside
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Kasid, U., Wang, FH. & Whiteside, T.L. Ionizing radiation and TNF-a stimulate gene expression of a Thr/Tyr -protein phosphatase HVH1 and inhibitory factor IkBa in human squamous carcinoma cells. Mol Cell Biochem 173, 197–201 (1997). https://doi.org/10.1023/A:1006892121504

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