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Multi-omics Characterization of Interaction-mediated Control of Human Protein Abundance levels.
Sousa, Abel; Gonçalves, Emanuel; Mirauta, Bogdan; Ochoa, David; Stegle, Oliver; Beltrao, Pedro.
Afiliación
  • Sousa A; Instituto de Investigação e Inovação em Saúde da Universidade do Porto (i3s), Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal; Graduate Program in Areas
  • Gonçalves E; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Mirauta B; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK.
  • Ochoa D; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK.
  • Stegle O; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK; ‡European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany; §Division of Computational Genomics and Systems Genetics, German Cancer Research
  • Beltrao P; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, Cambridge, UK. Electronic address: pbeltrao@ebi.ac.uk.
Mol Cell Proteomics ; 18(8 suppl 1): S114-S125, 2019 08 09.
Article en En | MEDLINE | ID: mdl-31239291
Proteogenomic studies of cancer samples have shown that copy-number variation can be attenuated at the protein level for a large fraction of the proteome, likely due to the degradation of unassembled protein complex subunits. Such interaction-mediated control of protein abundance remains poorly characterized. To study this, we compiled genomic, (phospho)proteomic and structural data for hundreds of cancer samples and find that up to 42% of 8,124 analyzed proteins show signs of post-transcriptional control. We find evidence of interaction-dependent control of protein abundance, correlated with interface size, for 516 protein pairs, with some interactions further controlled by phosphorylation. Finally, these findings in cancer were reflected in variation in protein levels in normal tissues. Importantly, expression differences due to natural genetic variation were increasingly buffered from phenotype differences for highly attenuated proteins. Altogether, this study further highlights the importance of posttranscriptional control of protein abundance in cancer and healthy cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Procesamiento Postranscripcional del ARN / Proteínas de Neoplasias / Neoplasias Límite: Humans Idioma: En Revista: Mol Cell Proteomics Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Procesamiento Postranscripcional del ARN / Proteínas de Neoplasias / Neoplasias Límite: Humans Idioma: En Revista: Mol Cell Proteomics Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos