The human papillomavirus type 16 E7 protein complements adenovirus type 5 E1A amino-terminus-dependent transactivation of adenovirus type 5 early genes and increases ATF and Oct-1 DNA binding activity

Abstract

We have previously shown that conserved region 1 (CR1) of the adenovirus type 5 (Ad5) E1A protein synergizes with CR3 in the transactivation of Ad5 early genes (H. K. Wong and E. B. Ziff, J. Virol. 68:4910-4920, 1994). CR1 lies within the E1A amino terminus and binds host regulatory proteins such as the RB protein, p107, p130, and p300. Since simian virus 40 (SV40) large T antigen and human papillomavirus type 16 (HPV16) E7 protein also bind host regulatory factors, we investigated whether these viral proteins can complement E1A mutants which are defective in early gene activation. We show that the HPV16 E7 protein but not SV40 T antigen can complement mutations in the Ad5 E1A CR1 in the transactivation of viral early promoters. The inability of SV40 T antigen to complement suggests that RB binding on its own is not sufficient for early promoter transactivation by the E1A amino terminus. Nuclear runoff assays show that complementation by HPV16 E7 restores the ability of the E1A mutants to stimulate early gene expression at the level of transcription. Furthermore, nuclear extracts from the E7-transformed cells show increased binding activity of ATF and Oct-1, factors that can recognize the elements of Ad5 early genes, consistent with gene activation by E1A and E7 at the transcriptional level.

Regulation of cyclin E gene expression by the human papillomavirus type 16 E7 oncoprotein

“…There is precedent for the ability of E7 to activate transcription factors distinct from E2F. Thus, evidence was presented for functional interactions between HPV-16 E7 and the transcription factors AP-1 (Antinore et al , 1996 ), ATF, Oct-1 (Wong & Ziff, 1996 ), Oct-4 (Brehm et al , 1999 ), TBP (Massimi et al , 1996 ) and the TBP-associated factor TAF110 (Mazzarelli et al , 1995 ). Our finding that multiple cis -acting elements in the cyclin E gene respond to expression of the E7 oncogene is reminiscent of the pleiotropic effects on gene expression exerted by the E1A gene of adenovirus 5, a well-known trans -activator of several cellular genes (for review, see Nevins, 1993 ).…”

Προσδιορισμός μεταλλάξεων στα γονίδια ras γενετικών αλλοιώσεων στο γονίδιο της p53 και των ιών του θηλώματος του ανθρώπου (HPV) σε κυτταρολογικό υλικό από γυναικολογικούς καρκίνους και προκαρκινικές αλλοιώσεις

“…H E7 πρωτεΐνη του HPV16 µπορεί να συµπληρώνει λειτουργίες του E1A που απαιτούνται για την διέγερση των πρώιµων υποκινητών του αδενοιού τύπου 5 (Wong, 1996).…”

Ο Ρόλος Του Ιού Θηλώματος Του Ανθρώπου (HPV) Σε Ακανθοκυτταρικό Καρκίνωμα Του Οισοφάγου (ESCC)

“…H E7 πρωτείνη του HPV16 μπορεί να συμπληρώνει λειτουργίες του E1A που απαιτούνται για την διέγερση των πρώιμων υποκινητών του αδενοιού τύπου 5 (Wong, 1996). Mε αυτό τον τρόπο σταθεροποιείται η συσχέτιση πρωτεινικών συμπλόκων που περιέχουν το c-jun ,με πλευρές ATF.…”