K-Ras Populates Conformational States Differently from Its Isoform H-Ras and Oncogenic Mutant K-RasG12D
نویسندگان
چکیده
منابع مشابه
Oncogenic Phenotypes in K-Ras Transformed Cells
Genetic mutations in K-Ras, an oncogene belonging to the Ras protein superfamily, are present in number of cancers, including over 90% of pancreatic and 50% of colorectal cancers. The mutated or oncogenic form of the K-Ras GTPase is perpetually locked in the GTP-bound active conformation, thereby inducing extreme and rapid cell proliferation as well as decreasing cell sensitivity to suspension-...
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Ras proteins regulate signaling cascades crucial for cell proliferation and differentiation by switching between GTP- and GDP-bound conformations. Distinct Ras isoforms have unique physiological functions with individual isoforms associated with different cancers and developmental diseases. Given the small structural differences among isoforms and mutants, it is currently unclear how these func...
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A considerable amount of evidence indicates that Ras signaling contributes to the development of endometrial cancer. We previously demonstrated that endometrial cancer cells carrying oncogenic [Val]K-ras were susceptible to apoptosis. The present study examined the role of K-and H-Ras in the induction of apoptosis using rat endometrial cells (RENT4 cells). We found that constitutively activated...
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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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UNLABELLED Activating point mutations in K-RAS are extremely common in cancers of the lung, colon, and pancreas and are highly predictive of poor therapeutic response. One potential strategy for overcoming the deleterious effects of mutant K-RAS is to alter its posttranslational modification. Although therapies targeting farnesylation have been explored, and have ultimately failed, the therapeu...
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ژورنال
عنوان ژورنال: Structure
سال: 2018
ISSN: 0969-2126
DOI: 10.1016/j.str.2018.03.018