title: Proteasome-mediated protein processing by bidirectional degradation initiated from an internal site.
abstract: The proteasome is a barrel-shaped protease that conceals its active sites within its central cavity. Proteasomes usually completely degrade substrates into small peptides, but in some cases, degradation yields biologically active protein fragments. Some transcription factors are generated from precursors by this activity, but the mechanism of proteasomal protein processing remains unclear. Here we show that proteasomal processing of the yeast NFkappaB-related transcription factors Spt23 and Mga2 is initiated by an internal cleavage, followed by bidirectional proteolysis of the polypeptides. Studies with protein fusions indicate that stable proteolytic fragments are generated if the protein contains tightly folded structures that prevent the complete degradation of the protein. Furthermore, we provide evidence that the ability of the proteasome to initiate proteolysis from an internal site and to proceed via bidirectional polypeptide degradation may be relevant for the complete degradation of proteins as well.
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Piwko
authors.forename: Stefan
authors.initials: S
authors.lastname: Jentsch
mesh_terms: D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: C542266:MGA2 protein, S cerevisiae; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C087570:SPT23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex