Novel Therapeutics for the Treatment of Burn Infection.

Burn injury continues to be a significant cause of morbidity and death, with infectious complications being the primary cause of death. Patients are susceptible to overwhelming infection secondary to both the physical breakdown of the skin and mucosal barrier and the immune dysfunction that accompanies the inflammatory response to a major burn. With resistance to traditional antibiosis looming as a serious threat to patient outcome, advancement in the treatment of burn infections is imperative.

Signaling and transcriptional changes critical for transformation of human cells by simian virus 40 small tumor antigen or protein phosphatase 2A B56gamma knockdown.

One set of genes sufficient for transformation of primary human cells uses the combination of Ha-Ras-V12, the telomerase catalytic subunit hTERT, SV40 large tumor antigen (LT), and SV40 small tumor antigen (ST). Whereas SV40 LT inactivates the retinoblastoma protein and p53, the contribution of ST is poorly understood. The essential helper function of ST requires a functional interaction with protein phosphatase 2A (PP2A).

Identification of specific PP2A complexes involved in human cell transformation.

The SV40 small t antigen (ST) interacts with the serine-threonine protein phosphatase 2A (PP2A). To investigate the role of this interaction in transformation, we suppressed the expression of the PP2A B56gamma subunit in human embryonic kidney (HEK) epithelial cells expressing SV40 large T antigen, hTERT, and H-RAS. Suppression of PP2A B56gamma expression inhibited PP2A-specific phosphatase activity similar to that achieved by ST and conferred the ability to grow in an anchorage-independent fashion and to form tumors.