The human T-lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia and lymphoma, produces a protein called p30 that is essential for the retrovirus to establish an infection. This study found that this viral protein targets two important cell proteins: ATM, a key player in a cell’s response to DNA damage, and REG-gamma, which marks proteins within the cell for destruction.
“Our findings suggest that the p30 viral protein prolongs the survival of host cells through this interaction with ATM and REG-gamma, and the longer a virus-infected cell survives, the better chance the virus has to spread, ” says principal investigator Michael Lairmore, DVM, PhD, professor of veterinary biosciences and associate director for shared resources at the OSUCCC – James.
The findings were published recently in the Journal of Biological Chemistry.
An estimated 20 million people worldwide are infected by HTLV-1, and about five percent of them will develop adult T-cell leukemia or lymphoma, or one of a variety of inflammatory disorders.
Lairmore and his colleagues used cell lines and a variety of biochemical assays to identify cellular binding partners of p30. They discovered the following:
- p30 specifically binds to cellular ATM (ataxia-telangiectasia mutated), a key regulator of DNA damage responses and cell cycle control, and to REG-gamma, a nuclear proteasome activator.
- Under stressful conditions, p30 levels are associated with lower ATM levels and increased cell survival.
- The expression of p30 changes in concert with expression of REG-gamma, suggesting that overexpression of REG-gamma enhances levels of p30.
- p30 forms a complex with ATM and REG-gamma.
Funding from the National Cancer Institute supported this research.
Other Ohio State researchers involved in this study were Rajaneesh Anupam, Antara Datta, Matthew Kesic, Kari Green-Church, Nikolozi Shkriabai and Mamuka Kvaratskhelia.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.