Article
Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras.
Molecular cell - 23 Dec 2011
Matallanas David, Romano David, Al-Mulla Fahd, O'Neill Eric, Al-Ali Waleed, Crespo Piero, Doyle Brendan, Nixon Colin, Sansom Owen, Drosten Matthias, Barbacid Mariano, Kolch Walter
Abstract excerpt
K-Ras mutations are frequent in colorectal cancer (CRC), albeit K-Ras is the only Ras isoform that can elicit apoptosis. Here, we show that mutant K-Ras directly binds to the tumor suppressor RASSF1A to activate the apoptotic MST2-LATS1 pathway. In this pathway LATS1 binds to and sequesters the ubiquitin ligase Mdm2 causing stabilization of the tumor suppressor p53 and apoptosis. However, mutant Ras also...
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