TY - JOUR
T1 - Characterisation of a nucleo-adhesome
AU - Byron, Adam
AU - Griffith, Billie G. C.
AU - Herrero, Ana
AU - Loftus, Alexander E. P.
AU - Koeleman, Emma S.
AU - Kogerman, Linda
AU - Dawson, John C.
AU - McGivern, Niamh
AU - Culley, Jayne
AU - Grimes, Graeme R.
AU - Serrels, Bryan
AU - Kriegsheim, Alex von
AU - Brunton, Valerie G.
AU - Frame, Margaret C.
N1 - Funding Information:
We thank Alfonso Bolado, Niall Quinn and Jimi Wills for assistance with MS data acquisition, Martin Lee for assistance with microscopy and Douglas Armstrong, Didier Devaurs, Noor Gammoh, Frederic Li Mow Chee, Roza Ali Masalmeh, Christina Schoenherr, Oksana Sorokina and Athanasia Yiapanas for discussions. The work was funded by Cancer Research UK (grants C157/A15703 and C157/A24837 to M.C.F.) and supported by the Wellcome Trust (multiuser equipment grant 208402/Z/17/Z to A.v.K.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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 define 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. Adding to nuclear FAK’s 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-5 work together in the nucleus, co-regulating a subset of genes transcriptionally. We demonstrate the principle that there are subcomplexes of nuclear adhesion proteins that cooperate to control transcription.
AB - 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 define 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. Adding to nuclear FAK’s 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-5 work together in the nucleus, co-regulating a subset of genes transcriptionally. We demonstrate the principle that there are subcomplexes of nuclear adhesion proteins that cooperate to control transcription.
U2 - 10.1038/s41467-022-30556-5
DO - 10.1038/s41467-022-30556-5
M3 - Article
C2 - 35650196
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3053
ER -