Cargando…
Signalling to eIF4E in cancer
Translational control plays a critical role in the regulation of gene expression in eukaryotes and affects many essential cellular processes, including proliferation, apoptosis and differentiation. Under most circumstances, translational control occurs at the initiation step at which the ribosome is...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613458/ https://www.ncbi.nlm.nih.gov/pubmed/26517881 http://dx.doi.org/10.1042/BST20150126 |
_version_ | 1782396281474252800 |
---|---|
author | Siddiqui, Nadeem Sonenberg, Nahum |
author_facet | Siddiqui, Nadeem Sonenberg, Nahum |
author_sort | Siddiqui, Nadeem |
collection | PubMed |
description | Translational control plays a critical role in the regulation of gene expression in eukaryotes and affects many essential cellular processes, including proliferation, apoptosis and differentiation. Under most circumstances, translational control occurs at the initiation step at which the ribosome is recruited to the mRNA. The eukaryotic translation initiation factor 4E (eIF4E), as part of the eIF4F complex, interacts first with the mRNA and facilitates the recruitment of the 40S ribosomal subunit. The activity of eIF4E is regulated at many levels, most profoundly by two major signalling pathways: PI3K (phosphoinositide 3-kinase)/Akt (also known and Protein Kinase B, PKB)/mTOR (mechanistic/mammalian target of rapamycin) and Ras (rat sarcoma)/MAPK (mitogen-activated protein kinase)/Mnk (MAPK-interacting kinases). mTOR directly phosphorylates the 4E-BPs (eIF4E-binding proteins), which are inhibitors of eIF4E, to relieve translational suppression, whereas Mnk phosphorylates eIF4E to stimulate translation. Hyperactivation of these pathways occurs in the majority of cancers, which results in increased eIF4E activity. Thus, translational control via eIF4E acts as a convergence point for hyperactive signalling pathways to promote tumorigenesis. Consequently, recent works have aimed to target these pathways and ultimately the translational machinery for cancer therapy. |
format | Online Article Text |
id | pubmed-4613458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-46134582015-10-23 Signalling to eIF4E in cancer Siddiqui, Nadeem Sonenberg, Nahum Biochem Soc Trans Biochemical Society Awards Translational control plays a critical role in the regulation of gene expression in eukaryotes and affects many essential cellular processes, including proliferation, apoptosis and differentiation. Under most circumstances, translational control occurs at the initiation step at which the ribosome is recruited to the mRNA. The eukaryotic translation initiation factor 4E (eIF4E), as part of the eIF4F complex, interacts first with the mRNA and facilitates the recruitment of the 40S ribosomal subunit. The activity of eIF4E is regulated at many levels, most profoundly by two major signalling pathways: PI3K (phosphoinositide 3-kinase)/Akt (also known and Protein Kinase B, PKB)/mTOR (mechanistic/mammalian target of rapamycin) and Ras (rat sarcoma)/MAPK (mitogen-activated protein kinase)/Mnk (MAPK-interacting kinases). mTOR directly phosphorylates the 4E-BPs (eIF4E-binding proteins), which are inhibitors of eIF4E, to relieve translational suppression, whereas Mnk phosphorylates eIF4E to stimulate translation. Hyperactivation of these pathways occurs in the majority of cancers, which results in increased eIF4E activity. Thus, translational control via eIF4E acts as a convergence point for hyperactive signalling pathways to promote tumorigenesis. Consequently, recent works have aimed to target these pathways and ultimately the translational machinery for cancer therapy. Portland Press Ltd. 2015-10-09 2015-10-01 /pmc/articles/PMC4613458/ /pubmed/26517881 http://dx.doi.org/10.1042/BST20150126 Text en © 2015 Authors; published by Portland Press Limited |
spellingShingle | Biochemical Society Awards Siddiqui, Nadeem Sonenberg, Nahum Signalling to eIF4E in cancer |
title | Signalling to eIF4E in cancer |
title_full | Signalling to eIF4E in cancer |
title_fullStr | Signalling to eIF4E in cancer |
title_full_unstemmed | Signalling to eIF4E in cancer |
title_short | Signalling to eIF4E in cancer |
title_sort | signalling to eif4e in cancer |
topic | Biochemical Society Awards |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613458/ https://www.ncbi.nlm.nih.gov/pubmed/26517881 http://dx.doi.org/10.1042/BST20150126 |
work_keys_str_mv | AT siddiquinadeem signallingtoeif4eincancer AT sonenbergnahum signallingtoeif4eincancer |