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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 and Peter J. Parker ()
Additional contact information
Silvia Martini: Protein Phosphorylation Laboratory, The Francis Crick Institute
Khalil Davis: Protein Phosphorylation Laboratory, The Francis Crick Institute
Rupert Faraway: RNA Network Laboratory, The Francis Crick Institute
Lisa Elze: Radboud University Medical Center
Nicola Lockwood: Protein Phosphorylation Laboratory, The Francis Crick Institute
Andrew Jones: Cell Cycle Laboratory, The Francis Crick Institute
Xiao Xie: Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University
Neil Q. McDonald: Signalling and Structural Biology Laboratory, The Francis Crick Institute
David J. Mann: Imperial College London
Alan Armstrong: Imperial College
Jernej Ule: RNA Network Laboratory, The Francis Crick Institute
Peter J. Parker: Protein Phosphorylation Laboratory, The Francis Crick Institute

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27189-5

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