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

ABSTRACT: The PKC-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 PKC cell cycle targets are involved. To address this, we developed a trapping strategy using UV-photocrosslinkable amino acids encoded in the PKC kinase domain. The validation of the mRNA binding protein SERBP1 as a PKC substrate revealed a series of mitotic events controlled by the catalytic form of PKC. PKC represses protein translation, altering SERBP1 binding to the 40S 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 PKC-controlled pathway exerting genome protection.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Andrew Jones  

LAB HEAD: Peter Parker

PROVIDER: PXD029091 | Pride | 2021-12-09

REPOSITORIES: Pride