Proximity labelling of pro-interleukin-1α reveals evolutionary conserved nuclear interactions
Interleukin (IL)-1α is a suggested dual-function cytokine that diverged from ILinterleukin-1β in mammals potentially by acquiring additional biological roles that relate to highly conserved regions in the pro-domain of interleukinIL-1α, including a nuclear localisation sequence (NLS) and histone ace...
Published in: | Nature Communications |
---|---|
Main Authors: | , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
2024
|
Subjects: | |
Online Access: | https://research.manchester.ac.uk/en/publications/e85954ce-7e00-4cd2-8f23-177830b088cf https://doi.org/10.1038/s41467-024-50901-0 |
Summary: | Interleukin (IL)-1α is a suggested dual-function cytokine that diverged from ILinterleukin-1β in mammals potentially by acquiring additional biological roles that relate to highly conserved regions in the pro-domain of interleukinIL-1α, including a nuclear localisation sequence (NLS) and histone acetyl transferase (HAT)-binding domains. Why evolution modified pro-ILinterleukin-1α’s subcellular location and protein interactome, and how this shaped ILinterleukin-1α’s intracellular role, is unknown. Here we show that TurboID proximity labelling with pro-ILinterleukin-1α suggestsed a nuclear role for pro-interleukinIL-1α that involves interaction with histone aceteyl transferasesHATs, including EP300. We also identifyied and validated inactivating mutations in the pro-interleukinIL-1α nuclear localisation sequence NLS of multiple mammalian species, including toothed whales, castorimorpha and marsupials. However, histone acetyl transferaseHAT-binding domains were are conserved in those species that haved lost pro-interleukinIL-1α nuclear localisation. Together, these data suggest that histone acetyl transferaseHAT binding and nuclear localisation occurred together, and that while some species lost the nuclear localisation sequenceNLS in their pro-interleukinIL-1α, histone acetyl transferaseHAT binding ability was maintained. The nuclear localisation sequenceNLS was lost from several distinct species at different evolutionary times, suggesting convergent evolution, and that the loss of the nuclear localisation sequence NLS confers some important biological outcome. |
---|