Translasome: Alpha and omega of protein metabolism
HOUSTON -- (October 9, 2009) -- A factor called eIF3 (eukaryotic initiation factor 3) critical to the translation of a gene's message into a protein is in fact only part of a large protein complex called the "translasome" because it contains all the proteins needed to regulate protein synthesis and protein degradation, said a Baylor College of Medicine expert.
"In the broader context, eIF3 may play a role in the control of breast cancer," said Dr. Eric Chang, associate professor of molecular and cellular biology at BCM and a member of the Lester and Sue Smith Breast Center. In mice, the gene encoding one of its subunits, eIF3e/Int6, is the site at which a mouse mammary tumor virus inserts itself to promote the cancer process. In human breast tumors, the expression of the INT6/EIF3E gene is also frequently down regulated, leading to low levels of its protein product in the cell.
Components of protein synthesis
In experiments designed to elucidate eIF3's molecular function, Chang and colleagues from the Burnham Institute for Medical Research in LaJolla, Calif., and the Israel Institute of Technology in Haifa isolated the molecule from yeast cells to look at all the proteins that interact with it. A report on their work appears in the current issue of the journal Molecular Cell.
"We found almost all the proteins needed for protein synthesis form a supercomplex, which we called the translasome," said Chang. "This suggests that all the components of protein synthesis need to be physically linked to work efficiently.
"We also found that the proteins needed to degrade proteins, called proteasomes, also form a complex with those needed to make proteins, a fact that seems counterintuitive," he said.
Not always simple process
However, protein synthesis in the cell is not always a simple or clean process.
"As with any job we might do, a lot of things do not pass quality control. The degradation machinery gives the cells the ability to correct many mistakes. When they can't, they send them to the proteasome to for degradation," said Chang.
The formation of the translasome supercomplex links the making of proteins closely to the disposal process in which the proteasome looks for misfolded or abnormal proteins and removes.
"It's as though the garbage can is right next to the assembly line," said Chang.
In fact, the translasome spatially coordinates steps in the synthesis of proteins, making it more efficient, said Chang and his colleagues in their report. Adding the degradation machinery insures the proteins are made correctly. Those that are not are degraded and discarded.
Activity in nucleus
Protein synthesis is thought to take place in the outer compartment of the cell, called the cytoplasm, as opposed to the nucleus in the center of the cell. However, in this study, they found that the translasome contains proteins that were thought to exist only in the nucleus. Furthermore, the translasome contains proteins whose function is to shuttle proteins into the nucleus. They also found that eIF3 can interact with these import proteins to control nuclear import of proteasomes. If translation proteins go into the nucleus together with proteasomes, this would raise the intriguing possibility that protein synthesis can also occur in the nucleus.
Others who took part in this research include Zhe Sha and Rodrigo Cabrera of BCM, Laurence Brill, Judith S. Scheliga and Dieter A. Wolf of the Burnham Institute for Medical Research in LaJolla, Calif., and Oded Kleifeld and Michael H. Glickman of the Israel Institute of Technology in Haifa.
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