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Translational control of the proteome: relevance to cancer
K Dua1, T M Williams, L Beretta
1Department of Microbiology and Immunology, University of Michigan, 1510 MSRB-I, 1150 W. Medical Ctr. Dr., Ann Arbor, MI 48109-0666, USA.
Abstract:
Translational control is an important but relatively unappreciated mechanism that regulates levels of protein products. In addition to a global translational control that regulates the cell's response to external stimuli such as growth factors, cytokines, stress and viral infections, selective translational control has recently been demonstrated to affect many genes related to growth and apoptotic processes. Modifications in the 5'untranslated region of these specific mRNAs may lead to an up-regulation of the protein product by as much as 100-fold. Translational infidelity has been reported in some human cancers for oncogenes such as c-myc and mdm2. Furthermore, modulation of selective translational control has also been demonstrated in cells over-expressing the translation initiation factor elF4E. Elevated levels of elF4E were found in a broad spectrum of solid tumors (breast, head and neck, colon and bladder carcinomas as well as in non-Hodgkin's lymphomas). Other translation initiation factors and translation components such as elongation factors and ribosomal proteins have also been reported to be overexpressed in some human tumors. This review discusses the relevance of these observations to a cell's proteome and for tumorigenesis and how the genomics and proteomics can be used to advance our understanding of the role of translational control in cancer.
Insights
Selective translational control, a key regulator of protein levels, impacts cancer development. Dysregulation of translation initiation factors like eIF4E is implicated in various human tumors, highlighting its oncogenic role.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- Translational control, a mechanism regulating protein production, is crucial for cellular responses to stimuli.
- Selective translational control affects genes involved in growth and apoptosis, with mRNA modifications potentially increasing protein output significantly.
- Aberrant translational control, including translational infidelity of oncogenes, is observed in human cancers.
Purpose of the Study:
- To review the significance of translational control in cancer biology.
- To explore the role of translation initiation factors, particularly eIF4E, in tumorigenesis.
- To discuss the application of genomics and proteomics in understanding translational control in cancer.
Main Methods:
- Literature review of studies on translational control mechanisms.
- Analysis of data on the expression levels of translation factors in various cancers.
- Discussion of the interplay between mRNA modifications, protein synthesis, and cancer development.
Main Results:
- Selective translational control can up-regulate protein products by up to 100-fold.
- Elevated levels of translation initiation factor eIF4E are prevalent in diverse solid tumors and lymphomas.
- Overexpression of other translation factors and ribosomal proteins is also noted in human tumors.
Conclusions:
- Dysregulation of translational control is a significant factor in tumorigenesis.
- The overexpression of translation initiation factors like eIF4E is a common event in cancer.
- Genomics and proteomics offer powerful tools to further elucidate the role of translational control in cancer.