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eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling.

Attar-Schneider O, Pasmanik-Chor M, Tartakover-Matalon S, Drucker L, Lishner M - Oncotarget (2015)

Bottom Line: Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets.We showed different imprints for eIF4E and eIF4GI in all assayed aspects.These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.

View Article: PubMed Central - PubMed

Affiliation: Oncogenetic Laboratory, Meir Medical Center, Kfar Saba, Israel.

ABSTRACT
Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis-multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.

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Decreased levels of eIF4E/eIF4GI upon their disassociation by 4EGIMM cell lines were treated with 4EGI (75 μM, 72 h) and immunoblotted for eIF4GI and peIF4E/Total eIF4E. Representative immunoblots (representative bands, right) and graphic presentations (Average value of MM cell lines, left, mean ± SE) are presented. HSC-70 served as a loading control. Statistically significant differences (*; p < 0.05, **; p < 0.01) are depicted.
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Figure 6: Decreased levels of eIF4E/eIF4GI upon their disassociation by 4EGIMM cell lines were treated with 4EGI (75 μM, 72 h) and immunoblotted for eIF4GI and peIF4E/Total eIF4E. Representative immunoblots (representative bands, right) and graphic presentations (Average value of MM cell lines, left, mean ± SE) are presented. HSC-70 served as a loading control. Statistically significant differences (*; p < 0.05, **; p < 0.01) are depicted.

Mentions: Surprisingly, we also observed a decrease in total eIF4E and eIF4GI levels upon their disassociation by 4EGI (Figure 6). To the best of our knowledge, this is a novel observation. Future studies are necessary to determine if the factors undergo increased degradation upon disassociation and whether the degradation is proteosome dependent.


eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling.

Attar-Schneider O, Pasmanik-Chor M, Tartakover-Matalon S, Drucker L, Lishner M - Oncotarget (2015)

Decreased levels of eIF4E/eIF4GI upon their disassociation by 4EGIMM cell lines were treated with 4EGI (75 μM, 72 h) and immunoblotted for eIF4GI and peIF4E/Total eIF4E. Representative immunoblots (representative bands, right) and graphic presentations (Average value of MM cell lines, left, mean ± SE) are presented. HSC-70 served as a loading control. Statistically significant differences (*; p < 0.05, **; p < 0.01) are depicted.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414192&req=5

Figure 6: Decreased levels of eIF4E/eIF4GI upon their disassociation by 4EGIMM cell lines were treated with 4EGI (75 μM, 72 h) and immunoblotted for eIF4GI and peIF4E/Total eIF4E. Representative immunoblots (representative bands, right) and graphic presentations (Average value of MM cell lines, left, mean ± SE) are presented. HSC-70 served as a loading control. Statistically significant differences (*; p < 0.05, **; p < 0.01) are depicted.
Mentions: Surprisingly, we also observed a decrease in total eIF4E and eIF4GI levels upon their disassociation by 4EGI (Figure 6). To the best of our knowledge, this is a novel observation. Future studies are necessary to determine if the factors undergo increased degradation upon disassociation and whether the degradation is proteosome dependent.

Bottom Line: Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets.We showed different imprints for eIF4E and eIF4GI in all assayed aspects.These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.

View Article: PubMed Central - PubMed

Affiliation: Oncogenetic Laboratory, Meir Medical Center, Kfar Saba, Israel.

ABSTRACT
Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis-multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.

Show MeSH
Related in: MedlinePlus