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

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posted on 26.11.2021, 14:04 by 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
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.

Funding

Crick (Grant ID: 10115, Grant title: Mcdonald FC001115) Crick (Grant ID: 10130, Grant title: Parker FC001130) Crick (Grant ID: 10121, Grant title: Nurse FC001121)

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