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Casein kinase 1ε promotes cell proliferation by regulating mRNA translation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Shin, Sejeong Wolgamott, Laura Roux, Philippe P. Yoon, Sang-oh |
| Copyright Year | 2014 |
| Abstract | Deregulation of translation initiation factors contributes to many pathogenic conditions, including cancer. Here, we report the definition of a novel regulatory pathway for translational initiation with possible therapeutic import in cancer. Specifically, we found that casein kinase 1ε (CK1ε) is highly expressed in breast tumors and plays a critical role in cancer cell proliferation by controlling mRNA translation. Eukaryotic translation initiation factor eIF4E, an essential component of the translation initiation complex eIF4F, is downregulated by binding the negative-acting factor 4E-BP1. We found that genetic or pharmacologic inhibition of CK1ε attenuated 4E-BP1 phosphorylation, thereby increasing 4E-BP1 binding to eIF4E and inhibiting mRNA translation. Mechanistic investigations showed that CK1ε interacted with and phosphorylated 4E-BP1 at two novel sites T41 and T50, which were essential for 4E-BP1 inactivation along with increased mRNA translation and cell proliferation. In summary, our work identified CK1ε as a pivotal regulator of mRNA translation and cell proliferation that acts by inhibiting 4E-BP1 function. As CK1ε is highly expressed in breast tumors, these findings offer an initial rationale to explore CK1ε blockade as a therapeutic strategy to treat cancers driven by deregulated mRNA translation. |
| Starting Page | 1931 |
| Ending Page | 1941 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/early/2013/11/16/0008-5472.CAN-13-1175.full.pdf |
| PubMed reference number | 24247720v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/0008-5472.CAN-13-1175 |
| DOI | 10.1158/0008-5472.CAN-13-1175 |
| Journal | Cancer research |
| Volume Number | 74 |
| Issue Number | 1 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Caseins Cell Proliferation Deregulation EIF4E wt Allele EIF4EBP1 wt Allele Eukaryotic Initiation Factor-4E Eukaryotic Translation Initiation Factor 4E, human Genetic Translation Process Inhibition Mammary Neoplasms Peptide Initiation Factors Pharmacology Protein Biosynthesis Transcription Initiation cancer cell casein kinase I negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay translation initiation complex |
| Content Type | Text |
| Resource Type | Article |
