A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division

Silvia Martini, Khalil Davis, Rupert Faraway, Lisa Elze, Nicola Lockwood, Andrew Jones, Xiao Xie, Neil Q. McDonald, David J. Mann, Alan Armstrong, Jernej Ule, Peter J. Parker*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    5 Citations (Scopus)

    Abstract

    The PKCε-regulated genome protective pathway provides transformed cells a failsafe to successfully complete mitosis. Despite the necessary role for Aurora B in this programme, it is unclear whether its requirement is sufficient or if other PKCε cell cycle targets are involved. To address this, we developed a trapping strategy using UV-photocrosslinkable amino acids encoded in the PKCε kinase domain. The validation of the mRNA binding protein SERBP1 as a PKCε substrate revealed a series of mitotic events controlled by the catalytic form of PKCε. PKCε represses protein translation, altering SERBP1 binding to the 40 S ribosomal subunit and promoting the assembly of ribonucleoprotein granules containing SERBP1, termed M-bodies. Independent of Aurora B, SERBP1 is shown to be necessary for chromosome segregation and successful cell division, correlating with M-body formation. This requirement for SERBP1 demonstrates that Aurora B acts in concert with translational regulation in the PKCε-controlled pathway exerting genome protection. [Abstract copyright: © 2021. The Author(s).]
    Original languageEnglish
    Article number6934
    Pages (from-to)6934
    JournalNature Communications
    Volume12
    Issue number1
    Early online date26 Nov 2021
    DOIs
    Publication statusPublished - Dec 2021

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