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Regulation of NF-κB2/p100 processing by its nuclear shuttling

Oncogene volume 22, pages 4868–4874 (2003)Cite this article

Abstract

Processing of the NF-κB2 precursor protein p100 to generate p52 is an important step of NF-κB regulation. This proteolytic event is tightly regulated by sequences located at the C-terminal portion of p100. Constitutive processing of p100 occurs in certain lymphoma cells due to the loss of its C-terminal regulatory domain, although the underlying mechanisms remain unknown. We show here that the constitutive processing of C-terminal truncation mutants of p100 is associated with their active nuclear translocation. Deletion of the C-terminal death domain of p100 triggers a low, but significant, level of nuclear translocation and processing. Disruption of the ankyrin-repeat domain of p100 further enhances its nuclear shuttling activity, which is again associated with elevated level of processing. More importantly, mutation of the nuclear localization signal (NLS) of p100 abolishes its processing, and this defect can be rescued by fusion of a heterologous NLS to the amino- or carboxyl-terminus of the p100 mutant. These results suggest that nuclear shuttling is a mechanism regulating the processing of NF-κB2/p100.

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Acknowledgements

We greatly acknowledge WC Greene and NR Rice for antibodies and expression vectors, M Yoshida for LMB, and Brian Wigdahl for the use of microscope. We also thank members of the Sun's laboratory for critical discussion of the work. This study was supported by Public Health Service grants 1R01 AI45045 and 1R01 CA94922 to S-CS.

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  1. Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Dr, Hershey, 17033, PA, USA

    Gongxian Liao & Shao-Cong Sun

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  1. Gongxian Liao
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  2. Shao-Cong Sun
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Correspondence to Shao-Cong Sun.

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Liao, G., Sun, SC. Regulation of NF-κB2/p100 processing by its nuclear shuttling. Oncogene 22, 4868–4874 (2003). https://doi.org/10.1038/sj.onc.1206761

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