The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

Rapp, Lisa; Liu, Yun; Hong, Yihui; Androphy, Elliot J.; Chen, Jason J.

doi:10.1038/sj.onc.1202373

Cited by 13 publications

(24 citation statements)

References 65 publications

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“…We previously showed that BPV-1 E6 was a strong inducer of apoptosis compared with other known pro-apoptosis viral oncogenes such as the polyomavirus middle T antigen (59). As shown in Fig.…”

Section: Resultsmentioning

confidence: 87%

“…Morphologically, PBE7 and PBAUE7 cells were indistinguishable from parental cells or retrovirus vector-infected PURO cells (59). For comparison, C127 cells expressing BPV-1 E6 (PBE6) were also examined (59).…”

Section: Resultsmentioning

confidence: 99%

“…For comparison, C127 cells expressing BPV-1 E6 (PBE6) were also examined (59). Within 24 h of confluence, PBE6 cells piled up and became highly spindle shaped, indicating a loss of contact inhibition as observed in focus formation assays with BPV-1 E6.…”

Section: Resultsmentioning

confidence: 99%

“…Expression of BPV-1 E7 Sensitizes C127 Cells to TNF-induced Cytolysis-We have previously observed that expression of BPV-1 E6 sensitizes C127 cells to TNF-induced apoptosis (59). To examine the TNF susceptibility of E7-expressing cells, PBE7 and PBAUE7 cells were treated with various concentrations of murine TNF, and cell viability was determined quantitatively by analysis of MTT conversion (61).…”

Section: Resultsmentioning

confidence: 99%

“…The release of AA also accompanies the lysis of cells rendered sensitive to TNF by inhibitors of transcription or translation and some viral proteins (64 -67). Our recent study showed that TNF-induced apoptosis in BPV-1 E6 cells was accompanied by increased release of arachidonic acid (59). Previous work has demonstrated that activation of the 85-kDa cytosolic phospholipase A 2 (cPLA 2 ) is required for TNF cytolysis (63,64,68).…”

Section: Sensitization Of E7-expressing Cells To Tnf-induced Apoptosimentioning

confidence: 99%

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

Liu¹,

Hong²,

Androphy³

et al. 2000

Journal of Biological Chemistry

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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 A 2 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.Papillomaviruses are small DNA viruses that infect various epithelial tissues, including the epidermis and the epithelial linings of the anogenital tract. Papillomaviruses replicate in the stratified layers of skin and mucosa and usually give rise to benign lesions such as warts or papillomas. Some animal papillomaviruses, including bovine papillomavirus type 1 (BPV-1), 1 induce fibropapillomas. Because of its ability to transform cells and to replicate its genome in established murine cell lines, BPV-1 has served as the prototype for studies of molecular biology of the papillomaviruses (for review see Ref. 1). Specific types ("high risk") of human papillomaviruses (HPV) infect the anogenital tract and are strongly associated with the development of cervical carcinoma (for review see Ref.2). The low risk HPV types, such as 6 and 11, are found associated primarily with benign lesions that rarely progress to cancer.Papillomavirus oncogenes manifest their transforming potential in various cell culture based assays and transgenic models (1). The transforming properties of high risk HPVs primarily reside in E6 and E7 genes. The ability of the E7 protein to associate with the cellular tumor suppressor pRB (3-5) has been suggested as a mechanism by which this viral protein promotes cell growth and proliferation. However, pRBindependent biological activities of E7 have been observed, and multiple additional cellular interactors of the viral proteins have also been identified (reviewed in Ref. 6). HPV-16 E7 induces DNA synthesis in quiescent or differentiated cells (7-10). HPV E7 cooperates with E6 to efficiently immortalize primary human epithelial cells (reviewed in Ref. 6). The expression of high ris...

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Sensitization Of E7-expressing Cells To Tnf-induced Apoptosimentioning

confidence: 99%

See 3 more Smart Citations

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

Liu¹,

Hong²,

Androphy³

et al. 2000

Journal of Biological Chemistry

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Bovine Papillomavirus Type 1 E6-Induced Sensitization to Apoptosis Is Distinct from Its Transforming Activity

Liu

Hong

et al. 2002

Virology

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The bovine papillomavirus type 1 (BPV-1) E6 oncoprotein induces tumorigenic transformation of murine C127 cells and stimulates transcription when targeted to a promoter. We have previously shown that C127 cells expressing BPV-1 E6 exhibited increased tumor necrosis factor alpha (TNF)-mediated apoptosis. To understand the mechanisms by which BPV-1 E6 sensitizes cells to apoptosis and to investigate the relevance of E6-enhanced apoptosis to its other biological activities, we analyzed a BPV-1 E6 mutant (491, with four amino acids deleted at the C-terminus) for its ability to sensitize C127 cells to apoptosis. The result was then compared with the E6 mutant's ability to transform cells, to activate transcription, and to associate with known cellular binding proteins. Our data indicated that the transcriptional activation function of BPV-1 E6 correlated with sensitization of cells to TNF-mediated apoptosis. Moreover, functions required for BPV-1 E6-mediated sensitization of cells to apoptosis are distinct from those required for transformation. A potential role of paxillin in E6 sensitization of cells to apoptosis is implicated. These results thus indicate that sensitization of cells to TNF-induced apoptosis represents a novel function of BPV-1 E6.

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Comprehensive characteristics of microRNA expression profile of equine sarcoids

et al. 2017

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The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

Cited by 13 publications

References 65 publications

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

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

Bovine Papillomavirus Type 1 E6-Induced Sensitization to Apoptosis Is Distinct from Its Transforming Activity

Comprehensive characteristics of microRNA expression profile of equine sarcoids

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