Answer the riddle of cancer for 10 years: eIF4E protein

Researchers have known for a long time that high levels of a specific protein in human cells are related to tumor growth, but the specific mechanism is not clear   Now, researchers from the school of life sciences at the University of California, Davis, have made a breakthrough discovery They have elucidated the mechanism of eukaryotic initiation factor 4E (eIF4E) protein's effect on cancer promoting messenger RNA molecules When translated, such mRNA can trigger uncontrolled cell replication, leading to cancer   The study, published in PNAS, answers a decade long scientific puzzle and is expected to accelerate the development of highly specific new cancer therapies that work only on growth accelerating cells, not on all cells   According to the researchers, eIF4E protein is the most important initiation factor in this cell signaling pathway, and a large amount of energy in the cell is involved in regulating its level and utilization The sudden discovery of this function will lead to a major change in the field of ideas; people can now try to study this new activity and its relationship with growth promotion and cancer   EIF4E was found to be elevated in 30% of all major cancers, and the protein has become a target of drug research EIF4E can combine the 5 'end cap structure of all mRNA, and clinical trials are currently being carried out for drugs that act on eIF4E, a long-term known function However, the cap binding activity of the protein does not fully explain its relationship with cancer   Scientists solved the mystery when they studied a region at the beginning of the mRNA chain This region of many oncogenic mRNA is much more complex than typical mRNA For these cancer promoting variants, before ribosome binding and starting to translate the genetic code into amino acids, and constructing our cell proteins, we must first untie this highly knotted region at the beginning of mRNA   In general, this knotted region prevents most ribosomes from initiating this process, so oncogenic mRNAs cannot be effectively translated However, in the presence of a high level of eIF4E, 4e binds to a complex to activate another protein 4a, which can then unravel the knot, translate the genetic code into a protein, and trigger tumor growth   After the researchers purified the components of eIF4E large protein complex and observed the activity of the complex without individual components, they made this breakthrough This is the first time that scientists have seen 4E stimulate 4A in this process
Without 4E, the complex was not active, the researchers said It has not been studied before without 4E because it is very difficult to separate single protein element In order to accomplish this task, it is very important to maintain the interaction between 4E and 4A complex If this connection is lost, the compound will stop working But if there are many 4E floating around in the cell, the compound loses one 4E and can easily find another   Now, in addition to the long-term known cap binding activity of 4E, researchers have supplemented its 4A stimulation and knotting activity   In view of the importance of the protein in cell physiology, the research findings, once confirmed, may modify textbooks In fact, in recent decades, no new research has been found on its function Next, the researchers plan to study the mechanism by which 4E, 4A and the rest of the complex work together to translate mRNA.