Transcriptional activation by the papillomavirus E6 zinc finger oncoprotein.

Abstract

The introduction of the bovine (BPV) or human papillomavirus E6 gene into susceptible cells can result in their transformation, but there are few clues to the mechanism of action of the E6 gene. The characteristic features of E6 proteins are their small size (approximately 150 amino acids) and the potential to form two large zinc fingers. To determine if E6 can function as a transcription factor, the BPV E6 gene was fused to the sequence specific DNA binding peptide encoded by the BPV E2 gene. This chimeric E6‐E2 protein trans‐activated promoters that incorporated E2 binding elements in both rodent cells and Saccharomyces cerevisiae. In the absence of E6‐E2 localization to the target promoter, trans‐activation did not occur. Alteration of the cysteine residues at the base of each finger abrogated the transcriptional activity of the E6‐E2 hybrids. These data demonstrated that the BPV E6 gene encodes a transcription activation domain and imply that a specific structure of the protein, most likely the zinc fingers, is critical for this function. Since these cysteine mutants are also transformation defective, E6 transcriptional functions may be required for its oncogenic activity.

Association of Bovine Papillomavirus Type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif

“…The results shown are the lacZ activity relative to that obtained with wild-type lexA-BE6 fusion. Because BE6-lexA fusions have endogenous transcriptional activation properties which are altered in BE6 mutants (Lamberti et al, 1990), OD405 values obtained in cultures expressing the empty B42-fusion vector alone were substracted from values obtained in the presence of B42-E6-AP or B42-paxillin fusions, to more closely approximate the lacZ activity resulting from the interaction of lexA-BE6 with E6-AP or paxillin. Transformation results re¯ect the induction of anchorage independent growth in nobel agar by BE6 mutants relative to wild-type BE6.…”

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

“…BPV-1 E6 stimulates transcription when targeted to a promoter (Lamberti et al, 1990), although cellular promoters responsive to BPV-1 E6 have not been identi®ed. Mutational analysis indicated that the transcriptional activation function of BPV-1 E6 is not su cient for cell transformation (Chen et al, 1997;Ned et al, 1997).…”

Sequence variations and viral genomic state of human papillomavirus type 16 in penile carcinomas from Ugandan patients.

“…The intrinsic binding affinity of HPV-16 E6 and E7 to the cellular tumour suppressors p53 and pRb, and the modulation of their expression by the LCR as well as by the P *( promoter, derepressed by the disruption of E2 during HPV integration into the cellular genome, have been correlated with their oncogenic properties in the pathogenesis of neoplasia of the female lower genital tract (Dyson et al, 1989 ;Werness et al, 1990 ;Scheffner et al, 1993Scheffner et al, , 1995Lambert & Howley, 1988 ;Lamberti et al, 1990 ;Schiller et al, 1989).…”