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

TY - JOUR

T1 - A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division

AU - Martini, Silvia

AU - Davis, Khalil

AU - Faraway, Rupert

AU - Elze, Lisa

AU - Lockwood, Nicola

AU - Jones, Andrew

AU - Xie, Xiao

AU - McDonald, Neil Q.

AU - Mann, David J.

AU - Armstrong, Alan

AU - Ule, Jernej

AU - Parker, Peter J.

N1 - Funding Information: We acknowledge the support of the Francis Crick Institute which receives its core funding from Cancer Research UK (CRUK) (FC001130), the UK Medical Research Council (MRC) (FC001130), and the Wellcome Trust (FC001130). This research was funded in whole, or in part, by the Wellcome Trust [FC001130]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We are grateful to the Schultz laboratory for providing the aaRS plasmid optimised to recognise AbK, and for the tRNAPyl which recognises the UAG codon. We acknowledge the support of the Light Microscopy, Proteomics and Peptide Chemistry STPs at the Francis Crick Institute. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - 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).]

AB - 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).]

UR - http://www.scopus.com/inward/record.url?scp=85119962682&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-27189-5

DO - 10.1038/s41467-021-27189-5

M3 - Article

AN - SCOPUS:85119962682

SN - 2041-1723

VL - 12

SP - 6934

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6934

ER -