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Mol. Cell. Biol., 05 1996, 2248-2254, Vol 16, No. 5
Copyright © 1996, American Society for Microbiology

A glycine-rich region in NF-kappaB p105 functions as a processing signal for the generation of the p50 subunit

L Lin and S Ghosh
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, New Haven, Connecticut 06520, USA.

Transcription factor NF-kappaB is generally considered to be a heterodimer with two subunits, p50 and p65. The p50 subunit has been suggested to be generated from its precursor, p105, via the ubiquitin- proteasome pathway. During processing, the C-terminal portion of p105 is rapidly degraded whereas the N-terminal portion (p50) is left intact. We report here that a 23-amino-acid, glycine-rich region (GRR) in p105 functions as a processing signal for the generation of p50. A GRR-dependent endoproteolytic cleavage downstream of the GRR releases p50 from p105, and this cleavage does not require any specific downstream sequences. p50 can be generated from chimeric precursor p105N-GRR-IkappaBalpha, while the C-terminal portion (IkappaBalpha) can also be recovered, suggesting that p105 processing includes two steps: a GRR-dependent endoproteolytic cleavage and the subsequent degradation of the C-terminal portion. We have also demonstrated that the GRR can direct a similar processing event when it is inserted into a protein unrelated to the NF-kappaB family and that it is therefore an independent signal for processing.


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