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Novel supercomplexes of the proteasome in regulation of protein biosynthesis
Author(s) -
Acs Klara,
Perreard Laurent,
Amir Omar,
Groisman Regina,
Gerber Scott,
Kisselev Alexei
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.605.6
Subject(s) - proteasome , initiation factor , translation (biology) , ribosome , protein biosynthesis , eukaryotic translation initiation factor 4 gamma , microbiology and biotechnology , eif4a1 , eif4ebp1 , protein degradation , biology , biochemistry , chemistry , rna , protein subunit , repressor , messenger rna , gene , gene expression
26S proteasomes are large (1.6–2.5 MDa) multi‐functional proteolytic complexes that degrade the majority of proteins in mammalian cells. Proteasome inhibitors selectively induce apoptosis of malignant cells; one compound of this class, Velcade, is being used for treatment of multiple myeloma and is in clinical trials for the treatment of other malignancies. We have recently discovered that the majority of proteasomes in mammalian cells exist in much larger complexes. We have purified these supercomplexes and analyze their composition by mass spectrometry. This proteomic analysis has identified ribosomes and multi‐subunit translation‐initiation factor eIF3, and several RNA‐binding proteins, as principal components of these complexes, along with proteasomes. Hence, we hypothesize that proteasomes play a role in the initiation of translation, most likely by destroying translation inhibitor proteins and/or RNA‐binding proteins that protect mRNA from degradation by nucleases but also act as translational repressors. We introduce in this work the proteasome involvement in translation initiation and the interaction of proteasome‐eIF3 supercomplexes. These findings reveal a novel and unexpected link between protein synthesis and degradation and indicate that connection between these processes is tighter than previously thought. This work was supported by NCCC 203959 to AK.