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J Biol Chem. 2007 Apr 13;282(15):10846-52. Epub 2007 Feb 5.

A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome.

Author information

1
Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.

Abstract

The proteasome usually completely degrades its target proteins, but it can also degrade a handful of proteins in a limited and site-specific manner. The molecular mechanism for such limited degradation is unknown. The repressor forms of Gli2 and Gli3 transcription factors are generated from their full-length proteins through limited proteasome-mediated protein degradation. In this study, we have taken advantage of the fact that Gli3 is efficiently processed, whereas Gli2 is not, and identified a region of approximately 200 residues in their C termini that determine differential processing of the two proteins. This region, named processing determinant domain, functions as a signal for protein processing in the context of not only Gli2 and Gli3 protein sequences but also a heterologous hybrid protein, which would otherwise be completely degraded by the proteasome. Thus, the processing determinant domain constitutes a novel domain that functions independently. Our findings explain, at the molecular level, why Gli2 and Gli3 are differentially processed and, more importantly, may help understand a probably general mechanism by which the proteasome degrades some of its target proteins partially rather than completely.

PMID:
17283082
DOI:
10.1074/jbc.M608599200
[Indexed for MEDLINE]
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