How some tumours grow cancerous?
Washington: Researchers have discovered the way the protein, eukaryotic initiation factor 4E (eIF4E), acts upon cancer-promoting messenger RNA molecules.
The results have solved a decades-long scientific mystery and may lead to new, highly specific cancer treatments that will act only on growth-promoting cells as opposed to all cells.
UC Davis assistant Professor Christopher Fraser said that this protein is one the most important initiation factors in this cellular pathway, and there is a lot of energy in the cell that goes into regulating the level and availability of it.
UC Davis graduate student Kateryna Feoktistova and Fraser solved its relationship to cancer while studying a region at the head of mRNA strands, where many cancer-promoting mRNA are much more complex than typical mRNA.
In the cancer-promoting variants, a highly knotted region at the start of the strand must be unwound before a ribosome can bind and begin translating the genetic code into the amino acids that build our cellular proteins.
Usually that knotted region prevents most of the ribosomes from starting the process, so cancer-promoting mRNAs aren`t translated effectively. But when high levels of eIF4E are present the 4E binds to a complex that activates another protein, 4A, which then is able to unwind the knot and translate the genetic code into proteins that can trigger tumor growth.
Feoktistova, a fifth-year Ph.D. student who also got her undergraduate degree at UC Davis, made the breakthrough when she purified the individual components of eIF4E`s larger protein complex and then observed the complex`s activity with individual parts missing. It was during this process that she first noticed 4E`s stimulation of 4A.
She said that it is necessary to maintain an interaction between 4E and the complex containing 4A in order to complete the unwinding.
Feoktistova said that if you lose this connection, you stall the complex.
She said that but if you have a lot of 4E floating around in the cell, and the complex loses a 4E, another one can be easily found.
The study has been published in the Proceedings of the National Academy of Sciences.