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  • The EMBO Journal (2006) 25, 1945 - 1956
  • doi:10.1038/sj.emboj.7601081

Published online: 13 April 2006

The 20S proteasome processes NF-kappaB1 p105 into p50 in a translation-independent manner

Anu K Moorthy, Olga V Savinova, Jessica Q Ho, Vivien Ya-Fan Wang, Don Vu and Gourisankar Ghosh

  1. Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA, USA

Correspondence to:

Gourisankar Ghosh, Department of Chemistry and Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0359, USA. Tel.: +1 858 822 0375; Fax: +1 858 822 1408; E-mail: gghosh@ucsd.edu

Received 26 July 2005; Accepted 15 March 2006

The NF-kappaB p50 is the N-terminal processed product of the precursor, p105. It has been suggested that p50 is generated not from full-length p105 but cotranslationally from incompletely synthesized molecules by the proteasome. We show that the 20S proteasome endoproteolytically cleaves the fully synthesized p105 and selectively degrades the C-terminus of p105, leading to p50 generation in a ubiquitin-independent manner. As small as 25 residues C-terminus to the site of processing are sufficient to promote processing in vivo. However, any p105 mutant that lacks complete ankyrin repeat domain (ARD) is processed aberrantly, suggesting that native processing must occur from a precursor, which extends beyond the ARD. Remarkably, the mutant p105 that lacks the internal region including the glycine-rich region (GRR) is completely degraded by 20S proteasome in vitro. This suggests that the GRR impedes the complete degradation of the p105 precursor, thus contributing to p50 generation.

  • Keywords:

    • 20S proteasome,
    • NF-kappaB,
    • p105,
    • processing,
    • ubiquitination