Cardiovirus leader proteins retarget host protein kinases toward alternative substrates to perturb nucleocytoplasmic traffic
(2023)
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- Authors
- Supervisors
- Michiels, Thomas
- Abstract
- Cardiovirus Leader (L) proteins are multifunctional proteins that interact with cellular protein kinases of the RSK family to counteract innate immune defenses. In the first part of this work, we deciphered the mechanism by which L induces a nucleocytoplasmic traffic perturbation. We showed that L brings RSK to the nuclear pore complex, where RSK directly phosphorylates FG-nucleoporins like NUP98 and NUP214. Thereby, the leader protein disturbs the nucleocytoplasmic transport of cellular proteins and RNA. In the second part of this thesis, we conducted a more detailed study of the different RSK isoforms. Using the analog-sensitive kinase technology, we identified novel RSK substrates and demonstrated that RSK1 and RSK4 share many common substrates, including RanBP3, PDCD4, IRS2 and ZC3H11A. Our results suggest that the specificity of the different RSK isoforms likely depends on their cellular or tissue-specific expression more than on their ability to accommodate a substrate.
- Affiliations
Citations
Lizcano Perret, B. (2023). Cardiovirus leader proteins retarget host protein kinases toward alternative substrates to perturb nucleocytoplasmic traffic. https://hdl.handle.net/2078.5/25069