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Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL

Oncogene volume 27, pages 6770–6781 (2008)Cite this article

Abstract

Misregulation of REL, a nuclear factor-κB family transcription factor, has been implicated in several human lymphoid malignancies. REL has a conserved N-terminal DNA-binding/dimerization domain called the Rel homology domain (RHD) and a C-terminal transactivation domain (TAD). Here, we define the sequences (amino acids (aa) 323–422) between the RHD and TAD as a REL inhibitory domain (RID) because deletion of these sequences increases both REL transactivation and DNA binding. Furthermore, we have characterized two REL mRNA splice variants that encode proteins with alterations near RID: one lacking exon 9 sequences (aa 308–330; RELΔ9) and one with an exonized Alu fragment insertion of 32 aa after aa 307 (REL+Alu). Deletion of RID or exon 9-encoded sequences increases transactivation by GAL4–REL by approximately threefold. Moreover, deletion of RID or exon 9 sequences increases transactivation by full-length REL from certain κB site-containing promoters and increases DNA binding by REL. Deletion of RID does not affect REL's ability to transform chicken spleen cells. Reverse transcriptase-polymerase chain reaction analysis of mRNA from both primary lymphoma samples and several transformed tissue culture cell lines indicates that the RELΔ9 splice variant is preferentially expressed in lymphoma, suggesting that the REL transcript lacking exon 9 could serve as a marker for certain types of lymphoid tumors.

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Acknowledgements

We thank Mike Garbati, Melanie Herscovitch, Daniel Starczynowski and Francis Wolenski for helpful discussions, and Michaela Buck, Karola Dorsch, Iwona Nerbas and Ingo Melzner for technical assistance. This work was supported by NIH Grant CA47763 (TDG) and a grant from Deutsche Krebshilfe (108060; TFB).

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  1. M A Weniger

    Present address: 3Current address: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20824-0105, USA.,

Authors and Affiliations

  1. Department of Biology, Boston University, Boston, MA, USA

    J R Leeman & T D Gilmore

  2. Department of Pathology, University of Ulm, Ulm, Germany

    M A Weniger & T F Barth

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Correspondence to T D Gilmore.

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Leeman, J., Weniger, M., Barth, T. et al. Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL. Oncogene 27, 6770–6781 (2008). https://doi.org/10.1038/onc.2008.284

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