Read on Twitter
Excited to see our ms now on bioRxiv in which we describe a regulated interaction of a caveolar coat protein, cavin3, with BRCA1. Led by @kerrieannmcmah2 and great collaboration with @MikeRMitolab @thestroudlab @TheYapLab and others. https://www.biorxiv.org/content/10.1101/2020.07.26.222158v2
Follow this thread for a brief summary
Cavin3, a component of cell surface caveolae, is lost in many human tumours. Quantitative whole cell SILAC-based proteomics of cavin3-null cells revealed a cluster of proteins linked to BRCA1 that were all down-regulated upon loss of Cavin3
Cavin3, a component of cell surface caveolae, is lost in many human tumours. Quantitative whole cell SILAC-based proteomics of cavin3-null cells revealed a cluster of proteins linked to BRCA1 that were all down-regulated upon loss of Cavin3
Are cavin3 and BRCA1 functionally linked? We showed that protein levels of cavin3 and BRCA1 are interdependent; loss of either one causes downregulation of the other. The two proteins can directly interact when synthesized in vitro and can associate when overexpressed in cellulo.
But the question remained whether cavin3 and BRCA1 can interact in vivo and, if so, how can this occur? At steady state, cavin3 associates with caveolae whereas BRCA1 localizes to the nucleus and cytosol.
We observed that cavin3 and BRCA1 were not associated under steady state conditions but only when cells were stressed, eg. after UV treatment. We proposed that the cavin3-BRCA1 interaction stabilizes BRCA1 against proteasomal degradation and facilitates the activity of BRCA1.
This could be shown by KO of cavin3 and BRCA1; the 2 proteins work together to regulate DNA repair or, in extreme conditions, to trigger apoptosis. Cavin3 loss in tumour cells causes disruption of these processes hindering DNA repair and allowing tumour cell survival.
