title: eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling.
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.
authors.affiliation: Oncogenetic Laboratory, Meir Medical Center, Kfar Saba, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Oshrat
authors.initials: O
authors.lastname: Attar-Schneider
authors.affiliation: Bioinformatics Unit, G.S.W. Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.affiliation: Oncogenetic Laboratory, Meir Medical Center, Kfar Saba, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shelly
authors.initials: S
authors.lastname: Tartakover-Matalon
authors.affiliation: Oncogenetic Laboratory, Meir Medical Center, Kfar Saba, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Drucker
authors.affiliation: Oncogenetic Laboratory, Meir Medical Center, Kfar Saba, Israel.|Department of Internal Medicine, Meir Medical Center, Kfar Saba, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Lishner
mesh_terms: D045744:Cell Line, Tumor; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015151:Immunoblotting; D009101:Multiple Myeloma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000502:physiology; D020543:Proteome; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: C113920:EIF4G1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D020543:Proteome; D034741:RNA, Small Interfering