Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

C-terminal truncation of Dlk/ZIP kinase leads to abrogation of nuclear transport and high apoptotic activity

Oncogene volume 18, pages 7212–7218 (1999)Cite this article

Abstract

Dlk (also termed ZIP kinase) is a novel serine/threonine kinase with a unique C-terminal domain that is rich in arginine and contains three putative NLS motifs and a functional lecuine zipper. Dlk is indeed localized in the nucleus where it shows a speckled distribution. To elucidate the biological functions of Dlk, we wanted to identify the signals relevant for nuclear transport and further the nuclear structures which Dlk binds to. Expression of various deletion and point mutations of Dlk as GFP fusion proteins revealed that the leucine zipper is required for association with speckles and the most C-terminal NLS is necessary and sufficient for nuclear transport. Interestingly, a C-terminal deletion mutant defective for nuclear transport exhibited a pronounced colocalization with actin filaments and, even more strikingly, was a very potent inducer of apoptosis. This apoptotic activity was abrogated, however, when this mutant was retargeted to the nucleus via a heterologous NLS from large T, indicating that Dlk only exerts an apoptotic activity in the cytoplasm. To identify the speckle like structures to which Dlk binds we performed immunofluorescence analyses with antibodies directed against representative marker proteins of replication, transcription, or splicing centers. None of these marker proteins revealed a colocalization with Dlk. Instead, we found a partial colocalization with PML bodies which seem to play a key role in regulation of apoptosis. Taken together, these data strongly suggest a functional role for Dlk in control of cell survival which is dependent on its subcellular localization.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 5
Figure 3
Figure 4
Figure 6

Similar content being viewed by others

References

  • Bloch DB, Chiche J-D, Orth D, DeLaMorte SM, Rosenzweig A and Bloch KD. . 1999 Mol. Cell Biol. 19: 4423–4430.

  • Cohen O, Feinstein E and Kimchi A. . 1997 EMBO J. 16: 998–1008.

  • Deiss LP, Feinstein E, Berissi H, Cohen O and Kimchi A. . 1995 Genes Dev. 9: 15–30.

  • Dragovich T, Rudin CM and Thompson CB. . 1998 Oncogene 17: 3207–3213.

  • Dyck JA, Maul GG, Miller Jr WH, Chen JD, Kakizuka A and Evans RM. . 1994 Cell 76: 333–343.

  • Emoto Y, Manome Y, Meinhardt G, Kisaki H, Kharbanda S, Robertson M, Ghayur T, Wong WW, Kamen R and Weichselbaum R. . 1995 EMBO J. 14: 6148–6156.

  • Fabrizio P, Laggerbauer B, Lauber J, Lane WS and Luhrmann R. . 1997 EMBO J. 16: 4092–4106.

  • Franke TF, Kaplan DR and Cantley LC. . 1997 Cell 88: 435–437.

  • Green DR. . 1998 Cell 94: 695–698.

  • Hozak P, Jackson DA and Cook PR. . 1994 J. Cell Sci. 107: 2191–2202.

  • Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K and Gotoh Y. . 1997 Science 275: 90–94.

  • Jarpe MB, Widmann C, Knall C, Schlesinger TK, Gibson S, Yujiri T, Fanger GR, Gelfand EW and Johnson GL. . 1998 Oncogene 17: 1475–1482.

  • Johnson NL, Gardner AM, Diener KM, Lange-Carter CA, Gleavy J, Jarpe MB, Minden A, Karin M, Zon LI and Johnson GL. . 1996 J. Biol. Chem. 271: 3229–3237.

  • Kawai T, Matsumoto M, Takeda K, Sanjo H and Akira S. . 1998 Mol. Cell. Biol. 18: 1642–1651.

  • Klotzsche O, Etzrodt D, Hohenberg H, Bohn W and Deppert W. . 1998 Oncogene 16: 3423–3434.

  • Kögel D, Plöttner O, Landsberg G, Christian S and Scheidtmann KH. . 1998 Oncogene 17: 2645–2654.

  • Lahti JM, Xiang J, Heath LS, Campana D and Kidd VJ. . 1995 Mol. Cell. Biol. 15: 1–11.

  • LaMorte VJ, Dyck JA, Ochs RL and Evans RM. . 1998 Proc. Natl. Acad. Sci. USA 95: 4991–4996.

  • Mills JC, Stone NL, Erhardt J and Pittman RN. . 1998 J. Cell. Biol. 140: 627–636.

  • Murata-Hori M, Suizu F, Iwasaki T, Kikuchi A and Hosoya H. . 1999 FEBS Lett. 451: 81–84.

  • Page G, Kögel D, Rangnekar V and Scheidtmann KH. . 1999 Oncogene 18: 7265–7273.

  • Quignon F, De Bels F, Koken M, Ameisen J-C and de The H. . 1998 Nature Genet. 20: 259–265.

  • Rangnekar V. . 1998 Apoptosis 3: 61–66.

  • Regnier CH, Song HY, Gao X, Goeddel DV, Cao Z and Rothe M. . 1997 Cell 90: 373–383.

  • Rittner K, Stöppler H, Pawlita M and Sczakiel G. . 1991 Methods Mol. Cell. Biol. 2: 176–181.

  • Spector DL, Fu XD and Maniatis T. . 1991 EMBO J. 10: 3467–3481.

  • Stanger BZ, Leder P, Lee TH, Kim E and Seed B. . 1995 Cell 81: 513–523.

  • Stuurman N, de Graaf A, Floore A, Josso A, Humbel B, de Jong L and van Driel R. . 1992 J. Cell. Sci. 101: 773–784.

  • Wang HG, Rapp UR and Reed JC. . 1996 Cell 87: 629–638.

  • Wang ZG, Ruggero D, Ronchetti S, Zhong S, Gaboli M, Rivi R and Pandolfi PP. . 1998 Nature Genet. 20: 266–272.

  • Wansink DG, Schul W, van der Kraan I, van Steensel B, van Driel R and de Jong L. . 1993 J. Cell Biol. 122: 283–293.

  • Widmann C, Gibson S and Johnson GL. . 1998 J. Biol. Chem. 273: 7141–7147.

  • Wulf E, Deboben A, Bautz FA, Faulstich H and Wieland T. . 1979 Proc. Natl. Acad. Sci. USA 76: 4498–4502.

  • Xia Z, Dickens M, Raingeaud J, Davis RJ and Greenberg ME. . 1995 Science 270: 1326–1331.

  • Yao R and Cooper GM. . 1995 Science 267: 2003–2006.

  • Zandi E, Chen Y and Karin M. . 1997 Science 281: 1360–1363.

Download references

Acknowledgements

We thank Dr S Stamm (Max-Planck-Institute of Neurobiology, Munich, Germany) for anti-PML and anti SC35 antibodies and helpful suggestions; Dr R Lührmann (Institute of Molecular Biology and Tumor Research, Marburg, Germany) for antibodies against U5-116 kD (snRNP), G Landsberg for his excellent technical assistance and R Kreutzfeld for help with computer processing of fluorescence pictures. This work was supported by the Deutsche Forschungsgemeinschaft, grant Sche246/4-3 and by means from the Fonds der Chemischen Industrie to KH Scheidtmann.

Author information

Authors and Affiliations

  1. Institute of Genetics, University of Bonn, Roemerstr. 164, Bonn, D-53117, Germany

    Donat Kögel, Hanna Bierbaum, Ute Preuss & Karl Heinz Scheidtmann

Authors
  1. Donat Kögel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanna Bierbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ute Preuss
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karl Heinz Scheidtmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kögel, D., Bierbaum, H., Preuss, U. et al. C-terminal truncation of Dlk/ZIP kinase leads to abrogation of nuclear transport and high apoptotic activity. Oncogene 18, 7212–7218 (1999). https://doi.org/10.1038/sj.onc.1203169

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203169

Keywords

This article is cited by

Search

Advanced search

Quick links