Characterisation of a nucleo-adhesome

Byron, A.; Griffith, B. G. C.; Herrero, A.; Loftus, A. E. P.; Koeleman, E. S.; Dawson, J. C.; Kogerman, L.; McGivern, N.; Culley, J.; Grimes, G. R.; Serrels, B.; von Kriegsheim, A.; Brunton, V. G.; Frame, M. C.

doi:10.1101/2021.08.31.458428

bioRxiv · 10.1101/2021.08.31.458428

Characterisation of a nucleo-adhesome

Byron, A.·Griffith, B. G. C.·Herrero, A.·Loftus, A. E. P.·Koeleman, E. S.·Dawson, J. C.·Kogerman, L.·McGivern, N.·Culley, J.·Grimes, G. R.·Serrels, B.·von Kriegsheim, A.·Brunton, V. G.·Frame, M. C.

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Abstract

In addition to central functions in cell adhesion signalling, integrin-associated proteins have wider roles at sites distal to adhesion receptors. In experimentally defined adhesomes, we noticed that there is clear enrichment of proteins that localise to the nucleus, and conversely, we now report that nuclear proteomes contain a class of adhesome components that localise to the nucleus. We here defined a nucleo-adhesome, providing experimental evidence for a remarkable scale of nuclear localisation of adhesion proteins, establishing a framework for interrogating nuclear adhesion protein functions. In adding to nuclear FAKs known roles in regulating transcription, we now show that nuclear FAK regulates expression of many adhesion-related proteins that localise to the nucleus and that nuclear FAK binds to the adhesome component and nuclear protein Hic-5. FAK and Hic-C work together in the nucleus, co-regulating a subset of genes transcriptionally. We describe the first nucleo-adhesome using a squamous cancer cell model, and demonstrate the new principle that there are nuclear adhesion protein subcomplexes that cooperate to control transcription. O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/458428v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1c841ceorg.highwire.dtl.DTLVardef@586a75org.highwire.dtl.DTLVardef@b54439org.highwire.dtl.DTLVardef@921537_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Byron, A., Griffith, B. G. C., Herrero, A., Loftus, A. E. P., Koeleman, E. S., Dawson, J. C., Kogerman, L., McGivern, N., Culley, J., Grimes, G. R., Serrels, B., von Kriegsheim, A., Brunton, V. G., Frame, M. C.. 2021-08-31. Characterisation of a nucleo-adhesome. https://doi.org/10.1101/2021.08.31.458428

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