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Role of the Ubiquitin—Proteasome Pathway in NF-κB Activation

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Ubiquitin and the Biology of the Cell

Abstract

The transcription factor NF-κB (nuclear factor κB) is a heterodimeric protein that plays a pivotal role in immune and inflammatory responses (for recent reviews see Verma et al., 1995; Finco and Baldwin, 1995; Thanos and Maniatis, 1995; Siebenlist et al., 1994; Baeuerle and Henkel, 1994). Both subunits of NF-κB (p50 and p65) are members of the Rel family of transcriptional activator proteins, but they differ in their modes of synthesis. The p65 subunit of NF-κB is produced as a mature protein, whereas the p50 subunit is generated by the proteolytic processing of a 105-kDa precursor protein (p105). The N-termini of p105 and p65 are homologous; both contain the Re1 homology region, which includes protein dimerization and DNA binding domains, and a nuclear localization signal (Fig. 1). In addition, the p65, but not the p50, subunit contains a transcriptional activation domain. The C-terminus of p105 is characterized by the presence of a sequence motif known as ankyrin repeats, and a PEST domain (Ghosh et al., 1990). Ankyrin repeats constitute a protein interaction domain (Gilligan and Bennett, 1993), and the PEST domain is associated with rapidly degraded proteins (Rechsteiner and Rogers, 1996). Proteolytic processing of p105 involves the degradation of the C-terminus containing the ankyrin repeats and PEST domain, leaving the 50-kDa N-terminal Re1 homology region intact (Fig. 1).

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  1. ProScript Inc., Cambridge, Massachusetts, 02139, USA

    Zhijian J. Chen

  2. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, 02138, USA

    Tom Maniatis

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  1. Zhijian J. Chen
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Editors and Affiliations

  1. Research Institute of Molecular Pathology, Vienna, Austria

    Jan-Michael Peters

  2. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

  3. Harvard Medical School, Boston, Massachusetts, USA

    Daniel Finley

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Chen, Z.J., Maniatis, T. (1998). Role of the Ubiquitin—Proteasome Pathway in NF-κB Activation. In: Peters, JM., Harris, J.R., Finley, D. (eds) Ubiquitin and the Biology of the Cell. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1922-9_10

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  • DOI: https://doi.org/10.1007/978-1-4899-1922-9_10

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