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:

The generation of nfkb2 p52: mechanism and efficiency

Oncogene volume 18, pages 6201–6208 (1999)Cite this article

Abstract

nfkb2 encodes two members of the NF-κB/Rel family of proteins: p52 and p100. The p100 polypeptide has been proposed to serve as a precursor of p52, which corresponds to the N-terminal half of p100. While p52 functions as a Rel transcription factor, the larger p100 protein acts as a cytoplasmic inhibitor of select NF-κB/Rel transcription factor complexes. Because of their distinct functions, we have studied the biochemical basis for the production of these two nfkb2-derived gene products. Like the p50 product of the nfkb1 gene, p52 is principally generated in a cotranslational manner involving proteolytic processing by the proteasome. The generation of p52 is dependent on a glycine-rich region (GRR) located upstream of the p52 C-terminus, and repositioning of this GRR alters the location of proteasome processing. In most cells, small amounts of p52 are produced relative to the levels of p100, unlike the usually balanced production of nfkb1-derived p50 and p105. Using p100/p105 chimeras containing different segments of the nfkb1 and nfkb2 genes, we have found that diminished p52 processing is a property conferred by peptide sequences located downstream of the GRR, flanking the site of p52 processing.

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

Abbreviations

RHD:

Rel homology domain

GRR:

glycine-rich region

NLS:

nuclear localization sequence

References

  • Baeuerle PA and Baltimore D. . 1996 Cell 87: 13–20.

  • Baeuerle PA and Henkel T. . 1994 Annu. Rev. Immunol. 12: 141–179.

  • Baumeister W, Walz J, Zuehl F and Seemueller E. . 1998 Cell 92: 367–380.

  • Baldwin AJ. . 1996 Annu. Rev. Immunol. 14: 649–683.

  • Barnes PJ and Karin M. . 1997 N. Engl. J. Med. 336: 1066–1071.

  • Beraud C, Sun SC, Ganchi P, Ballard DW and Greene WC. . 1994 Mol. Cell. Biol. 14: 1374–1382.

  • Betts JC and Nabel GJ. . 1996 Mol. Cell. Biol. 16: 6363–6371.

  • Bours V, Burd PR, Brown K, Villalobos J, Park S, Ryseck RP, Bravo R, Kelly K and Siebenlist U. . 1992 Mol. Cell. Biol. 12: 685–695.

  • Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K and Siebenlist U. . 1993 Cell 72: 729–739.

  • Brown K, Gerstberger S, Carlson L, Franzoso G and Siebenlist U. . 1995 Science 267: 1485–1488.

  • Caamano JH, Rizzo CA, Durham SK, Barton DS, Raventos SC, Snapper CM and Bravo R. . 1998 J. Exp. Med. 187: 185–196.

  • Crowley KS, Reinhart GD and Johnson AE. . 1993 Cell 73: 1101–1115.

  • Duckett CS, Perkins ND, Kowalik TF, Schmid RM, Huang ES, Baldwin AJ and Nabel GJ. . 1993 Mol. Cell. Biol. 13: 1315–1322.

  • Feuillard J, Korner M, Israel A, Vassy J and Raphael M. . 1996 Eur. J. Immunol. 26: 2547–2551.

  • Franzoso G, Carlson L, Poljak L, Shores EW, Epstein S, Leonardi A, Grinberg A, Tran T, Scharton KT, Anver M, Love P, Brown K and Siebenlist U. . 1998 J. Exp. Med. 187: 147–159.

  • Frydman J, Nimmesgern E, Ohtsuka K and Hartl FU. . 1994 Nature 370: 111–117.

  • Ghosh S, Gifford AM, Riviere LR, Tempst P, Nolan GP and Baltimore D. . 1990 Cell 62: 1019–1029.

  • Gilmore TD, Koedood M, Piffat KA and White DW. . 1996 Oncogene 13: 1367–1378.

  • Grumont RJ and Gerondakis S. . 1994 Cell 5: 1321–1331.

  • Ishikawa H, Carrasco D, Claudio E, Ryseck RP and Bravo R. . 1997 J. Exp. Med. 7: 999–1014.

  • Kieran M, Blank V, Logeat F, Vandekerckhove J, Lottspeich F, Le BO, Urban MB, Kourilsky P, Baeuerle PA and Israel A. . 1990 Cell 62: 1007–1018.

  • Lin L and Ghosh S. . 1996 Mol. Cell. Biol. 16: 2248–2254.

  • Lin L, DeMartino GN, Greene WC. . 1998 Cell 92: 819–828.

  • Liou HC, Sha WC, Scott ML and Baltimore D. . 1994 Mol. Cell. Biol. 14: 5349–5359.

  • Mercurio F, DiDonato JA, Rosette C and Karin M. . 1993 Genes Dev. 7: 705–718.

  • Neri A, Chang CC, Lombardi L, Salina M, Corradini P, Maiolo AT, Chaganti RS and Dalla FR. . 1991 Cell 67: 1075–1087.

  • Neri A, Fracchiolla NS, Migliazza A, Trecca D and Lombardi L. . 1996 Leuk. Lymphoma 23: 43–48.

  • Rice NR, MacKichan ML and Israel A. . 1992 Cell 71: 243–253.

  • Schmid RM, Perkins ND, Duckett CS, Andrews PC and Nabel GJ. . 1991 Nature 352: 733–736.

  • Siebenlist U, Franzoso G and Brown K. . 1994 Annu. Rev. Cell. Biol. 10: 405–455.

  • Zhang Q, Didonato JA, Karin M and McKeithan TW. . 1994 Mol. Cell. Biol. 14: 3915–3926.

Download references

Acknowledgements

We thank R Benitez for assistance in reagent preparation; C de Noronha and S Ferrell for helpful discussions; J Carroll, N Shea, S Gonzales, and C Goodfellow for assistance in the preparation of the figures; S Ordway and G Howard for editorial assistance; and R Givens for preparation of the manuscript. This work was supported in part by a grant from the UCSF-GIVI Center for AIDS Research (P30A127763). R Geleziunas is supported by a Centennial Fellowship from the Medical Research Council of Canada.

Author information

Authors and Affiliations

  1. Gladstone Institute of Virology and Immunology, University of California, San Francisco, 94141-9100, California, CA, USA

    Marina Heusch, Li Lin, Romas Geleziunas & Warner C Greene

  2. Department of Medicine, University of California, San Francisco, 94141-9100, California, CA, USA

    Warner C Greene

  3. Department of Microbiology, University of California, San Francisco, 94141-9100, California, CA, USA

    Warner C Greene

  4. Department of Immunology, University of California, San Francisco, 94141-9100, California, CA, USA

    Warner C Greene

Authors
  1. Marina Heusch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Romas Geleziunas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Warner C Greene
    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

Heusch, M., Lin, L., Geleziunas, R. et al. The generation of nfkb2 p52: mechanism and efficiency. Oncogene 18, 6201–6208 (1999). https://doi.org/10.1038/sj.onc.1203022

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203022

Keywords

This article is cited by

Search

Advanced search

Quick links