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:

DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC

Oncogene volume 18, pages 2589–2597 (1999)Cite this article

Abstract

DEF-3(g16/NY-LU-12) encodes a novel RNA binding protein isolated by positional cloning from an SCLC homozygous deletion region in 3p21.3 and, in parallel, as a differentially expressed gene during myelopoiesis from FDCPmix-A4 cells. DEF-3(g16/NY-LU-12) is ubiquitously expressed during mouse embryogenesis and in adult organs while human hematopoietic tissues showed differential expression. The mouse and human proteins are highly conserved containing two RNA recognition motifs (RRMs) and other domains associated with RNA binding and protein-protein interactions. A database search identified related proteins in human, rat, C. elegans and S. pombe including the 3p21.3 co-deleted gene, LUCA15. Recombinant proteins containing the RRMs of DEF-3(g16/NY-LU-12) and LUCA15 specifically bound poly(G) RNA homopolymers in vitro. These RRMs also show similarity to those of the Hu protein family. Since anti-Hu RRM domain antibodies are associated with an anti-tumor effect and paraneoplastic encephalomyelitis, we tested sera from Hu syndrome patients with the RRMs of DEF-3(g16/NY-LU-12) and LUCA15. These were non-reactive. Thus, DEF-3(g16/NY-LU-12) and LUCA15 represent members of a novel family of RNA binding proteins with similar expression patterns and in vitro RNA binding characteristics. They are co-deleted in some lung cancers and immunologically distinct from the Hu proteins.

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 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Amasino R. . 1986 Analytic. Biochem. 152: 304–307.

  • Bardwell VJ and Treisman R. . 1994 Genes Dev. 8: 1664–1677.

  • Birney E, Kumar S and Krainer AR. . 1993 Nucl. Acids Res. 21: 5803–5816.

  • Burd CG and Dreyfuss G. . 1994 Sci. 265: 615–620.

  • Cairns P, Okami K, King P, Bonacum J, Ahrendt S, Wu L, Mao L, Jen J and Sidransky D. . 1997 Cancer Res. 57: 5356–5359.

  • Dalmau J, Graus F, Rosenblum MK and Posner JB. . 1992 Medicine (Balt.) 71: 59–72.

    Article  CAS  Google Scholar 

  • Daly MC, Xiang RH, Buchhagen D, Hensel CH, Garcia DK, Killary AM, Minna JD and Naylor SL. . 1993 Oncogene 8: 1721–1729.

  • Dong S, Zhu J, Reid A, Strutt P, Guidez F, Zhong HJ, Wang ZY, Licht J, Waxman S and Chomienne C. . 1996 Proc. Natl. Acad. Sci. USA 93: 3624–3629.

  • Gao FB, Carson CC, Levine T and Keene JD. . 1994 Proc. Natl. Acad. Sci. USA 91: 11207–11211.

  • Graus F, Dalmau J, Rene R, Tora M, Malats N, Verschuuren JJ, Cardenal F, Vinolas N, Garcia del Muro J, Vadell C, Mason WP, Rosell R, Posner JB and Real FX. . 1997 J. Clin. Oncol. 15: 2866–2872.

  • Grondin B, Bazinet M and Aubry M. . 1996 J. Biol. Chem. 271: 15458–15467.

    Article  CAS  Google Scholar 

  • Gure AO, Altorki NK, Stockert E, Scanlan MJ, Old LJ and Chen Y-T. . 1998 Cancer Res. 58: 1034–1041.

  • Inoue A, Takahashi KP, Kimura M, Watanabe T and Morisawa S. . 1996 Nucl. Acids Res. 24: 2990–2997.

  • Kaplan J and Calame K. . 1997 Nucl. Acids Res. 25: 1108–1116.

  • Kenan DJ, Query CC and Keene JD. . 1991 Trends Biochem. Sci. 16: 214–220.

  • Kim YJ and Baker BS. . 1993 Mol. Cell Biol. 13: 174–183.

  • Kok K, van den Berg A, Veldhuis PM, van der Veen AY, Franke M, Schoenmakers EF, Hulsbeek MM, van der Hout AH, de Leij L, van de Ven W and Buys CHCM. . 1994 Cancer Res. 54: 4183–4187.

  • Levine TD, Gao F, King PH, Andrews LG and Keene JD. . 1993 Mol. Cell. Biol. 13: 3494–3504.

    Article  CAS  Google Scholar 

  • Numoto M, Niwa O, Kaplan J, Wong KK, Merrell K, Kamiya K, Yanagihara K and Calame K. . 1993 Nucl. Acids Res. 21: 3767–3775.

  • Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN and Reddy ES. . 1994 Oncogene 9: 3087–3097.

  • Okano HJ and Darnell RB. . 1997 J. Neurosci. 17: 3024–3037.

    Article  CAS  Google Scholar 

  • Oubridge C, Ito N, Evans PR, Teo CH and Nagai K. . 1994 Nature 372: 432–438.

    Article  CAS  Google Scholar 

  • Roche J, Boldog F, Robinson M, Robinson L, Varella-Garcia M, Swanton M, Waggoner B, Fishel R, Franklin W, Gemmill R and Drabkin H. . 1996 Oncogene 12: 1289–1297.

  • Sekido Y, Bader SA, Carbone DP, Johnson BE and Minna JD. . 1994 Cancer Res. 54: 4988–4992.

  • Singh R, Valcarcel J and Green MR. . 1995 Sci. 268: 1173–1176.

  • van den Berg A, Hulsbeek MF, de Jong D, Kok K, Veldhuis PM, Roche J and Buys CH. . 1996 Genes Chrom. Cancer 15: 64–72.

  • Varella-Garcia M, Rao K, Rabenhorst SH, Wiest J, Drabkin H, Gemmill R, Anderson MW and Franklin WA. . 1997 Lung Cancer 18: 140.

    Article  Google Scholar 

  • Wei MH, Latif F, Bader S, Kashuba V, Chen JY, Duh FM, Sekido Y, Lee CC, Geil L, Kuzmin I, Zabarovsky E, Klein G, Zbar B, Minna J and Lerman MI. . 1996 Cancer Res. 56: 1487–1492.

  • Wu L, Nichogiannopoulou A, Shortman K and Georgopoulos K. . 1997 Immunity 7: 483–492.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr C Korch for assistance with nucleotide sequencing through the auspices of the University of Colorado Cancer Center DNA Sequencing Core, supported by P30 CA 46934 and Dr C Kappen, Scottsdale, AZ for providing EST clone pCHR15-5. This investigation was supported by grants CA58187 and DAMD17-94J-4391 from the NIH and Department of Defense and the Special Trustees of the Middlesex Hospital, UCH and UCL Medical School (CRDC) and The Wellcome Trust.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, 80262, Colorado, USA

    Harry A Drabkin, James D West, Paul Erickson, Roser Calvo & Robert M Gemmill

  2. Department of Experimental Neurooncology, University Hospital Münster, Paediatric Haematology/Oncology, Münster, Germany

    Marc Hotfilder

  3. Department of Medicine, The Windeyer Institute of Medical Sciences, University College London, London, UK

    Yee M Heng & Fred Sablitzky

  4. Department of Medicine, Hospital de Badalona Germans Trias i Pujol, Barcelona, Spain

    Roser Calvo

  5. Department of Neurology, Laboratory of Molecular Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, NY, USA

    Josep Dalmau

Authors
  1. Harry A Drabkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James D West
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marc Hotfilder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yee M Heng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roser Calvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Josep Dalmau
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robert M Gemmill
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fred Sablitzky
    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

Drabkin, H., West, J., Hotfilder, M. et al. DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC. Oncogene 18, 2589–2597 (1999). https://doi.org/10.1038/sj.onc.1202601

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202601

Keywords

This article is cited by

Search

Advanced search

Quick links