A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome Academic Article uri icon

Overview

MeSH Major

  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Proteasome Endopeptidase Complex

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.

publication date

  • April 13, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M608599200

PubMed ID

  • 17283082

Additional Document Info

start page

  • 10846

end page

  • 52

volume

  • 282

number

  • 15