Proteomic analysis of the human KEOPS complex identifies C14ORF142 as a core subunit homologous to yeast Gon7
| Autor: | Rachel K. Szilard, Hao Huang, Timothy F. Ng, Amy A. Caudy, Frank Sicheri, Anne-Claude Gingras, Pierre Maisonneuve, Rob C. Laister, Leo C. K. Wan, Jean-Philippe Lambert, Noah Manczyk, Daniel Durocher |
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| Rok vydání: | 2016 |
| Předmět: |
Proteomics
0301 basic medicine TRNA modification Saccharomyces cerevisiae Proteins Protein subunit Saccharomyces cerevisiae Mutant medicine.disease_cause Cell Line Open Reading Frames 03 medical and health sciences Protein Interaction Mapping Genetics medicine Humans Amino Acid Sequence Protein Interaction Maps Molecular Biology Mutation biology biology.organism_classification Intrinsically Disordered Proteins Protein Subunits Open reading frame 030104 developmental biology Multiprotein Complexes Transfer RNA |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The KEOPS/EKC complex is a tRNA modification complex involved in the biosynthesis of N6-threonylcarbamoyladenosine (t6A), a universally conserved tRNA modification found on ANN-codon recognizing tRNAs. In archaea and eukaryotes, KEOPS is composed of OSGEP/Kae1, PRPK/Bud32, TPRKB/Cgi121 and LAGE3/Pcc1. In fungi, KEOPS contains an additional subunit, Gon7, whose orthologs outside of fungi, if existent, remain unidentified. In addition to displaying defective t6A biosynthesis, Saccharomyces cerevisiae strains harboring KEOPS mutations are compromised for telomere homeostasis, growth and transcriptional co-activation. To identify a Gon7 ortholog in multicellular eukaryotes as well as to uncover KEOPS-interacting proteins that may link t6A biosynthesis to the diverse set of KEOPS mutant phenotypes, we conducted a proteomic analysis of human KEOPS. This work identified 152 protein interactors, one of which, C14ORF142, interacted strongly with all four KEOPS subunits, suggesting that it may be a core component of human KEOPS. Further characterization of C14ORF142 revealed that it shared a number of biophysical and biochemical features with fungal Gon7, suggesting that C14ORF142 is the human ortholog of Gon7. In addition, our proteomic analysis identified specific interactors for different KEOPS subcomplexes, hinting that individual KEOPS subunits may have additional functions outside of t6A biosynthesis. |
| Databáze: | OpenAIRE |
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