Benzamides and benzamidines as specific inhibitors of epidermal growth factor receptor and v-Src protein tyrosine kinases

2004 ◽  
Vol 12 (13) ◽  
pp. 3529-3542 ◽  
Author(s):  
Toru Asano ◽  
Tomohiro Yoshikawa ◽  
Taikou Usui ◽  
Hiroshi Yamamoto ◽  
Yoshinori Yamamoto ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Protein Tyrosine Kinases ◽  
Protein Tyrosine ◽  
Epidermal Growth ◽  
Specific Inhibitors

Salicylanilides as Inhibitors of the Protein Tyrosine Kinase Epidermal Growth Factor Receptor.

ChemInform ◽  
2004 ◽  
Vol 35 (29) ◽  
Author(s):  
Christoph Liechti ◽  
Urs Sequin ◽  
Guido Bold ◽  
Pascal Furet ◽  
Thomas Meyer ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Protein Tyrosine ◽  
Epidermal Growth

scholarly journals RNA Interference Screen Identifies Usp18 as a Regulator of Epidermal Growth Factor Receptor Synthesis

2009 ◽  
Vol 20 (6) ◽  
pp. 1833-1844 ◽  
Author(s):  
Jason E. Duex ◽  
Alexander Sorkin
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Mrna Translation ◽  
Small Interfering Rnas ◽  
Catalytic Cysteine ◽  
Elevated Expression ◽  
Epidermal Growth

Elevated expression of epidermal growth factor receptor (EGFR) contributes to the progression of many types of cancer. Therefore, we developed a high-throughput screen to identify proteins that regulate the levels of EGFR in squamous cell carcinoma. Knocking down various ubiquitination-related genes with small interfering RNAs led to the identification of several novel genes involved in this process. One of these genes, Usp18, is a member of the ubiquitin-specific protease family. We found that knockdown of Usp18 in several cell lines reduced expression levels of EGFR by 50–80%, whereas the levels of other receptor tyrosine kinases remained unchanged. Overexpression of Usp18 elevated EGFR levels in a manner requiring the catalytic cysteine of Usp18. Analysis of metabolically radiolabeled cells showed that the rate of EGFR protein synthesis was reduced up to fourfold in the absence of Usp18. Interestingly, this dramatic reduction occurred despite no change in the levels of EGFR mRNA. This suggests that depletion of Usp18 inhibited EGFR mRNA translation. In fact, this inhibition required the presence of native 5′ and 3′ untranslated region sequences on EGFR mRNA. Together, our data provide evidence for the novel mechanism of EGFR regulation at the translational step of receptor synthesis.

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