MyJournals Home  

RSS FeedsEstrogen receptor {alpha} promotes protein synthesis by fine-tuning the expression of the eukaryotic translation initiation factor 3 subunit f (eIF3f) [Protein Synthesis and Degradation] (Journal of Biological Chemistry)

 
 

15 february 2019 00:01:32

 
Estrogen receptor {alpha} promotes protein synthesis by fine-tuning the expression of the eukaryotic translation initiation factor 3 subunit f (eIF3f) [Protein Synthesis and Degradation] (Journal of Biological Chemistry)
 




Approximately two thirds of all breast cancer cases are estrogen receptor (ER)-positive. The treatment of this breast cancer subtype with endocrine therapies is effective in the adjuvant and recurrent settings. However, their effectiveness is compromised by the emergence of intrinsic or acquired resistance. Thus, identification of new molecular targets can significantly contribute to the development of novel therapeutic strategies. In recent years, many studies have implicated aberrant levels of translation initiation factors in cancer etiology and provided evidence that identifies these factors as promising therapeutic targets. Accordingly, we observed reduced levels of the eIF3 subunit eIF3f in ER-positive breast cancer cells compared with ER-negative cells, and determined that low eIF3f levels are required for proper proliferation and survival of ER-positive MCF7 cells. The expression of eIF3f is tightly controlled by ER? at the transcriptional (genomic pathway) and translational (nongenomic pathway) level. Specifically, estrogen-bound ER? represses transcription of the EIF3F gene, while promoting eIF3f mRNA translation. To regulate translation, estrogen activates the mTORC1 pathway, which enhances the binding of eIF3 to the eIF4F complex and, consequently, the assembly of the 48S preinitiation complexes and protein synthesis. We observed preferential translation of mRNAs with highly structured 5-UTRs that usually encode factors involved in cell proliferation and survival (e.g. cyclin D1 and survivin). Our results underscore the importance of estrogen-ER?-mediated control of eIF3f expression for the proliferation and survival of ER-positive breast cancer cells. These findings may provide rationale for the development of new therapies to treat ER-positive breast cancer.


Del.icio.us Digg Facebook Google StumbleUpon Twitter
 
19 viewsCategory: Biochemistry
 
Transcriptional regulators involved in responses to volatile organic compounds in plants [Signal Transduction] (Journal of Biological Chemistry)
Deuterium induces a distinctive Escherichia coli proteome that correlates with the reduction in growth rate [Genomics and Proteomics] (Journal of Biological Chemistry)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Biochemistry

Use these buttons to bookmark us:
Del.icio.us Digg Facebook Google StumbleUpon Twitter


Valid HTML 4.01 Transitional
Copyright © 2008 - 2019 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Travel Photos Nachrichten Indigonet Finances Leer Mandarijn