Brother’s Keeper: Wild-Type Mutant K-Ras Dimers Limit Oncogenesis
نویسندگان
چکیده
منابع مشابه
Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras.
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, mutan...
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متن کاملThe differential effects of wild-type and mutated K-Ras on MST2 signaling are determined by K-Ras activation kinetics.
K-Ras is frequently mutated in human cancers. Mutant (mt) K-Ras can stimulate both oncogenic transformation and apoptosis through activation of extracellular signal-regulated kinase (ERK) and AKT pathways and the MST2 pathway, respectively. The biological outcome is determined by the balance and cross talk between these pathways. In colorectal cancer (CRC), a K-Ras mutation is negatively correl...
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The cellular Ras is known to play an important role in cellular proliferation mediated by growth factor receptor. Evidence also points to its role in growth arrest. Substantiated proof for growth-suppressive activity of wild-type Ras comes from studies that showed 1) loss of wild-type ras allele in tumors, 2) suppression of growth in cells transformed by oncogenic ras upon overexpression of wil...
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ژورنال
عنوان ژورنال: Cell
سال: 2018
ISSN: 0092-8674
DOI: 10.1016/j.cell.2018.01.019