Researchers find function of proteins that can enhance the progression of viruses and cancer cells

August 16, 2010

In a discovery that has implications for developing treatments against cancer and potentially deadly viruses, researchers at SUNY Downstate Medical Center have discovered the function of proteins that can enhance the progression of certain viruses and cancer cells. Their findings were published in the journal Genes and Development.

According to Tatyana Pestova, PhD, DSc, assistant professor of , and Christopher Hellen, DPhil, associate professor of cell biology, "The significance of our work is that we have identified proteins (Ligatin, MCT-1 and DENR) that can substitute for the activity of one or more canonical initiation factors in the initiation and ribosome recycling stages of eukaryotic . These factors act either individually (Ligatin) or together (MCT-1 and DENR) to substitute for eIF2 in promoting initiation of translation on a specific subset of mRNAs under conditions when translation is globally repressed. These observations are clinically relevant with respect to (a) viral infections and (b) cancer pathogenesis." Maxim Skabkin, PhD, a research scientist in the Department of Cell Biology, is the lead author of the paper.

The cellular response to counteract viral infection involves activation of pathways that "shut off" translation by phosphorylating eIF2, preventing it from recruiting initiator tRNA to the ribosome. Some viral mRNAs continue to be translated at the same or a reduced rate under these conditions, including those of virus, human rotaviruses (a major cause of acute, frequently fatal, gastroenteritis in infants), coronaviruses (including SARS), and alphaviruses (e.g. Sindbis virus).

The authors reported a novel eIF2-independent mode of translation initiation in which Ligatin alone or MCT-1 and DENR together promote binding of initiator tRNA to specific ribosomal initiation complexes, and found that this mechanism functions very efficiently for Sindbis virus and to a lesser extent for and related pathogenic viruses. This novel initiation mechanism is thus a potential target for therapeutic inhibition to counteract viral infection.

This eIF2-independent mode of initiation is likely a cellular mechanism that has been co-opted by viruses. MCT-1 (multiple copies in T-cell lymphoma-1) has previously been reported to act at the translational level to increase cell proliferation and survival and to enhance the invasiveness of , but how it functions was not known. It is an oncogene that is over-expressed in lung cancer tissues and has been implicated in the development of human T-cell and B-cell lymphomas.

Dr. Hellen adds, "Our identification of a specific role for MCT-1 in promoting eIF2-independent initiation on specific mRNAs could account for its oncogenic activity by promoting the preferential translation of a subset of cancer-related mRNAs into proteins that promote angiogenesis, tumor cell survival, transformation, and metastasis."

Related Stories

Recommended for you

US regulators approve 2nd gene therapy for blood cancer

October 19, 2017
U.S. regulators on Wednesday approved a second gene therapy for a blood cancer, a one-time, custom-made treatment for aggressive lymphoma in adults.

New study reveals breast cancer cells recycle their own ammonia waste as fuel

October 19, 2017
Breast cancer cells recycle ammonia, a waste byproduct of cell metabolism, and use it as a source of nitrogen to fuel tumor growth, report scientists from Harvard Medical School in the journal Science.

New findings explain how UV rays trigger skin cancer

October 18, 2017
Melanoma, a cancer of skin pigment cells called melanocytes, will strike an estimated 87,110 people in the U.S. in 2017, according to the Centers for Disease Control and Prevention. A fraction of those melanomas come from ...

Drug yields high response rates for lung cancer patients with harsh mutation

October 18, 2017
A targeted therapy resurrected by the Moon Shots Program at The University of Texas MD Anderson Cancer Center has produced unprecedented response rates among patients with metastatic non-small cell lung cancer that carries ...

Possible new immune therapy target in lung cancer

October 18, 2017
A study from Bern University Hospital in collaboration with the University of Bern shows that so-called perivascular-like cells from lung tumors behave abnormally. They not only inadequately support vascular structures, but ...

Many pelvic tumors in women may have common origin—fallopian tubes

October 17, 2017
Most—and possibly all—ovarian cancers start, not in ovaries, but instead in the fallopian tubes attached to them.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.