Martini, S;
Davis, K;
Faraway, R;
Elze, L;
Lockwood, N;
Jones, A;
Xie, X;
... Parker, PJ; + view all
(2021)
A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division.
Nature Communications
, 12
(1)
, Article 6934. 10.1038/s41467-021-27189-5.
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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.
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