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• W2158720439 endingPage "7390" @default.
• W2158720439 startingPage "7377" @default.
• W2158720439 abstract "Cot, initially identified as an oncogene in a truncated form, is a mitogen-activated protein kinase kinase kinase implicated in cellular activation and proliferation. Here, we show that this truncation of Cot results in a 10-fold increase in its overall kinase activity through two different mechanisms. Truncated Cot protein exhibits a lower turnover rate (half-life, 95 min) than wild-type Cot (half-life, 35 min). The degradation of wild-type and truncated Cot can be specifically inhibited by proteasome inhibitors in situ. The 20S proteasome also degrades wild-type Cot more efficiently than the truncated protein. Furthermore, the amino acid 435 to 457 region within the wild-type Cot COOH-terminal domain confers instability when transferred to the yellow fluorescent protein and targets this fusion protein to degradation via the proteasome. On the other hand, the kinase specific activity of wild-type Cot is 3.8-fold lower than that of truncated Cot, and it appears that the last 43 amino acids of the wild-type Cot COOH-terminal domain are those responsible for this inhibition of kinase activity. In conclusion, these data demonstrate that the oncogenic activity of truncated Cot is the result of its prolonged half-life and its higher kinase specific activity with respect to wild-type Cot." @default.
• W2158720439 created "2016-06-24" @default.
• W2158720439 creator A5016349252 @default.
• W2158720439 creator A5033224033 @default.
• W2158720439 creator A5052617220 @default.
• W2158720439 creator A5059912529 @default.
• W2158720439 creator A5087100680 @default.
• W2158720439 date "2003-10-01" @default.
• W2158720439 modified "2023-09-26" @default.
• W2158720439 title "The COOH-Terminal Domain of Wild-Type Cot Regulates Its Stability and Kinase Specific Activity" @default.
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• W2158720439 doi "https://doi.org/10.1128/mcb.23.20.7377-7390.2003" @default.
• W2158720439 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/230324" @default.
• W2158720439 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14517305" @default.
• W2158720439 hasPublicationYear "2003" @default.
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