DNA Damage Regulates Translation through β-TRCP Targeting of CReP

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Approximately 600 human genes encode enzymes that act as ubiquitin ligases, which facilitate the transfer of the small protein ubiquitin to thousands of substrate proteins; “tagging” with ubiquitin often promotes the degradation of the substrate by the proteasome. In this paper, we adapt a technique called Ligase Trapping for use in mammalian cells. Ligase Trapping is a highly accurate method for determining which substrates are targeted by a ubiquitin ligase. Here we use it to identify new substrates of the human cell cycle regulator βTRCP. Our screen was indeed highly accurate, as we were able to validate 88% of the candidate substrates we identified by mass spectrometry. Some of these new substrates were unstable proteins that were stabilized by inhibition of βTRCP, or of the entire class of ubiquitin ligases of which βTRCP is a part. However, others appear to be stable or redundantly-targeted substrates, which have been more difficult to identify with current techniques. This suggests that Ligase Trapping will be able to reliably identify new substrates of human ubiquitin ligases. Further, one of the new βTRCP substrates, CReP, is specifically depleted upon DNA damage, and depletion of CReP contributes to inactivation of the translational machinery upon DNA damage.

Vyšlo v časopise: DNA Damage Regulates Translation through β-TRCP Targeting of CReP. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005292
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005292

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