Cancer-causing virus exploits key cell-survival proteins

"The longer a virus-infected cell survives, the better chance the virus has to spread,” says principal investigator Michael Lairmore, DVM, PhD.

The human T-lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukaemia 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 5% of them will develop adult T-cell leukaemia or lymphoma, or one of a variety of inflammatory disorders.

Identifying cellular binding partners of p30

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 over expression of REG-gamma enhances levels of p30.

• p30 forms a complex with ATM and REG-gamma.

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 Centre - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centres 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.

Source: Ohio State University