EIF4E (eukaryotic translation initiation factor 4E)

Review on EIF4E (eukaryotic translation initiation factor 4E), with data on DNA, on the protein encoded, and where the gene is implicated

The effects of antiviral treatment on breast cancer cell line

Background: Recent studies have revealed the positive antiproliferative and cytotoxic effects of antiviral agents in cancer treatment. The real effect of adjuvant antiviral therapy is still controversial due to the lack of studies in biochemical mechanisms. Here, we studied the effect of the antiviral agent acyclovir on morphometric and migratory features of the MCF7 breast cancer cell line. Molecular levels of various proteins have also been examined. Methods: To evaluate and assess the effect of antiviral treatment on morphometric, migratory and other cellular characteristics of MCF7 breast cancer cells, the following experiments were performed: (i) MTT assay to measure the viability of MCF7 cells; (ii) Colony formation ability by soft agar assay; (iii) Morphometric characterization by immunofluorescent analysis using confocal microscopy; (iv) wound healing and transwell membrane assays to evaluate migration and invasion capacity of the cells; (v) ELISA colorimetric assays to assess expression levels of caspase-3, E-cadherin and enzymatic activity of aldehyde dehydrogenase (ALDH). Results: We demonstrate the suppressive effect of acyclovir on breast cancer cells. Acyclovir treatment decreases the growth and the proliferation rate of cells and correlates with the upregulated levels of apoptosis associated cytokine Caspase-3. Moreover, acyclovir inhibits colony formation ability and cell invasion capacity of the cancer cells while enhancing the expression of E-cadherin protein in MCF7 cells. Breast cancer cells are characterized by high ALDH activity and associated with upregulated proliferation and invasion. According to this study, acyclovir downregulates ALDH activity in MCF7 cells. Conclusions: These results are encouraging and demonstrate the possibility of partial suppression of cancer cell proliferation using an antiviral agent. Acyclovir antiviral agents have a great potential as an adjuvant therapy in the cancer treatment. However, more research is necessary to identify relevant biochemical mechanisms by which acyclovir induces a potent anti-cancer effect

A TFEB nuclear export signal integrates amino acid supply and glucose availability

How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3β phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognized nuclear export signal (NES). Importantly, GSK3β is inactivated by AKT in response to mTORC2 signaling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle

A TFEB nuclear export signal integrates amino acid supply and glucose availability

How cells coordinate the response to fluctuating carbon and nitrogen availability required to maintain effective homeostasis is a key issue. Amino acid limitation that inactivates mTORC1 promotes de-phosphorylation and nuclear translocation of Transcription Factor EB (TFEB), a key transcriptional regulator of lysosome biogenesis and autophagy that is deregulated in cancer and neurodegeneration. Beyond its cytoplasmic sequestration, how TFEB phosphorylation regulates its nuclear-cytoplasmic shuttling, and whether TFEB can coordinate amino acid supply with glucose availability is poorly understood. Here we show that TFEB phosphorylation on S142 primes for GSK3β phosphorylation on S138, and that phosphorylation of both sites but not either alone activates a previously unrecognized nuclear export signal (NES). Importantly, GSK3β is inactivated by AKT in response to mTORC2 signaling triggered by glucose limitation. Remarkably therefore, the TFEB NES integrates carbon (glucose) and nitrogen (amino acid) availability by controlling TFEB flux through a nuclear import-export cycle