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; Peter J Parker

doi:10.1038/s41467-021-27189-5

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

Nat Commun. 2021 Nov 26;12(1):6934. doi: 10.1038/s41467-021-27189-5.

Authors

Silvia Martini^#¹, Khalil Davis^#¹, Rupert Faraway^{2

3}, Lisa Elze⁴, Nicola Lockwood¹, Andrew Jones⁵, Xiao Xie⁶, Neil Q McDonald⁷, David J Mann⁸, Alan Armstrong⁹, Jernej Ule^{2

3}, Peter J Parker^{10

11}

Affiliations

¹ Protein Phosphorylation Laboratory, The Francis Crick Institute, London, UK.
² RNA Network Laboratory, The Francis Crick Institute, London, UK.
³ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
⁴ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
⁵ Cell Cycle Laboratory, The Francis Crick Institute, London, UK.
⁶ Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
⁷ Signalling and Structural Biology Laboratory, The Francis Crick Institute, London, UK.
⁸ Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
⁹ Department of Chemistry, Imperial College, London, UK.
¹⁰ Protein Phosphorylation Laboratory, The Francis Crick Institute, London, UK. peter.parker@crick.ac.uk.
¹¹ School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Campus, London, UK. peter.parker@crick.ac.uk.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aurora Kinase B / metabolism
Chromosome Segregation*
HEK293 Cells
HeLa Cells
Humans
Mitosis*
Protein Biosynthesis*
Protein Kinase C-epsilon / metabolism*
RNA-Binding Proteins / metabolism*

Substances

RNA-Binding Proteins
SERBP1 protein, human
AURKB protein, human
Aurora Kinase B
PRKCE protein, human
Protein Kinase C-epsilon

Abstract

Publication types

MeSH terms

Substances

Grants and funding