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RASSF effectors couple diverse RAS subfamily GTPases to the Hippo pathway

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Science Signaling  13 Oct 2020:
Vol. 13, Issue 653, eabb4778
DOI: 10.1126/scisignal.abb4778

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Diversity among RASSFs

GTPases of the RAS superfamily couple diverse stimuli to specific downstream pathways by interacting with various effectors that contain RAS-association (RA) domains, such as RA domain family (RASSF) proteins. Although RAS signaling is often associated with cellular proliferation, coupling to the RASSFs has been reported to promote apoptosis. Through binding studies in vitro and in cells, Dhanaraman et al. found that RASSFs 1 to 6 interacted with the Hippo ortholog MST1, and RASSFs 8 to 10 interacted with the p53 regulators ASPP1 and ASPP2. Only RASSF5 interacted with HRAS and KRAS, and RASSF1 interacted with members of the RGK subfamily of RAS GTPases and inhibited nuclear localization of the Hippo-responsive transcription factor YAP. This systematic analysis of RASSF binding partners is a valuable first step in defining the molecular mechanisms through which these RAS effectors couple different RAS family members to proapoptotic pathways.

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