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J. Biol. Chem., Vol. 275, Issue 40, 30894-30900, October 6, 2000

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Rb-independent Induction of Apoptosis by Bovine Papillomavirus Type 1 E7 in Response to Tumor Necrosis Factor ^*

Yun Liu, Yihui Hong, Elliot J. Androphy^§, and Jason J. Chen^¶

From the  Department of Dermatology, New England Medical Center and Tufts University School of Medicine and the ^§ Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111

Bovine papillomavirus type 1 (BPV-1) is a small DNA virus that causes fibropapillomas of the host. BPV-1 has served as the prototype for studies of the molecular biology of the papillomaviruses. BPV-1 efficiently induces anchorage-independent growth and focus formation in murine C127 cells. The transforming properties of BPV-1 primarily reside in two genes, E5 and E6. Each of these genes is sufficient to transform cells. Although no independent transformation activity has been detected for E7, it was shown to be required for full transformation of C127 by BPV-1. We investigated the biological activities of BPV-1 E7 in several assays. Our results indicate that expression of BPV-1 E7 sensitizes cells to tumor necrosis factor  (TNF)-induced apoptosis. The TNF-induced apoptosis in E7-expressing cells was accompanied by increased release of arachidonic acid, indicating that phospholipase A₂ was activated. Unlike the E7 proteins from the cancer-related human papillomaviruses, the BPV-1 E7 protein does not associate efficiently with the retinoblastoma protein (pRB) in vitro, nor does it significantly affect the pRB levels in cultured cells. Furthermore, BPV-1 E7 sensitizes Rb-null cells to TNF-induced apoptosis. These studies indicate that BPV-1 E7 can sensitize cells to apoptosis through mechanisms that are independent of pRB.

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