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Disruption of ubiquitin mediated proteolysis is a widespread mechanism of tumorigenesis

View ORCID ProfileFrancisco Martínez-Jiménez, View ORCID ProfileFerran Muiños, View ORCID ProfileErika Lopez-Arribillaga, View ORCID ProfileNuria Lopez-Bigas, View ORCID ProfileAbel Gonzalez-Perez
doi: https://doi.org/10.1101/507764
Francisco Martínez-Jiménez
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
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  • ORCID record for Francisco Martínez-Jiménez
Ferran Muiños
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
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Erika Lopez-Arribillaga
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
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Nuria Lopez-Bigas
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
2Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
3Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
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  • For correspondence: nuria.lopez@irbbarcelona.org abel.gonzalez@irbbarcelona.org
Abel Gonzalez-Perez
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
2Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
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  • For correspondence: nuria.lopez@irbbarcelona.org abel.gonzalez@irbbarcelona.org
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Abstract

E3 ligases and degrons --the sequences they recognize in target proteins-- are key parts of the ubiquitin-mediated proteolysis system. There are several examples of alterations of these two components of the system that play a role in cancer. Here, we uncovered the landscape of the contribution of such alterations to tumorigenesis across cancer types. We first systematically identified novel instances of degrons across the human proteome using a random forest classifier, and validated them exploiting somatic mutations across more than 7,000 tumors. We detected signals of positive selection across these novel degrons and revealed new instances involved in cancer development. Overall, we estimated that at least one in seven driver mutations across primary tumors affect either degrons or E3 ligases.

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Posted December 28, 2018.
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Disruption of ubiquitin mediated proteolysis is a widespread mechanism of tumorigenesis
Francisco Martínez-Jiménez, Ferran Muiños, Erika Lopez-Arribillaga, Nuria Lopez-Bigas, Abel Gonzalez-Perez
bioRxiv 507764; doi: https://doi.org/10.1101/507764
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Disruption of ubiquitin mediated proteolysis is a widespread mechanism of tumorigenesis
Francisco Martínez-Jiménez, Ferran Muiños, Erika Lopez-Arribillaga, Nuria Lopez-Bigas, Abel Gonzalez-Perez
bioRxiv 507764; doi: https://doi.org/10.1101/507764

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