The human papillomavirus 18 (HPV 18) long control region contains promoter and enhancer elements whose activity is restricted to several human cell lines of epithelial origin. This enhancer possesses a considerable constitutive activity which is further stimulated in the presence of the E2 trans‐activating protein of bovine papillomavirus 1 (BPV1). Surprisingly the same BPV1 protein strongly repressed transcription from the genuine HPV18 enhancer‐promoter DNA sequences. We suggest that binding of several molecules of E2 protein between the viral CAAT and TATA elements sterically hinders transcription initiation from this promoter, while the same DNA–protein assembly stimulates the SV40 promoter when cloned in an enhancer configuration upstream of this heterologous promoter. Unlike BPV1‐E2 the homologous E2 gene product does not seem to strongly modulate viral transcription. Finally the BPV1‐E2 gene product may repress some essential viral or host genes, since we failed to isolate HeLa cells expressing BPV1‐E2.

(Androphy et al., 1987; Dostatni et al., 1988;McBride Sylvain Goyat, Moshe Yaniv and et al., 1989). Franç oise Thierry 1Bovine papillomavirus type 1 (BPV-1) has been studied condylomas. In HPV18, the viral transforming genes E6 level of cell death by apoptosis and G 1 arrest. Overand E7 are expressed from a single promoter, termed P 105 , expression of a p53 trans-dominant-negative mutant which is regulated by an upstream 800 bp long control abolished both E2-induced p53 transcriptional activregion (LCR) (Thierry et al., 1987a). This region contains ation and E2-mediated G 1 growth arrest, but showed a keratinocyte-specific enhancer, upstream of promoter no effect on E2-triggered apoptosis. These results sugelements (TATA and Sp1) crucial for transcription (Garciagest that the effects of E2 on cell cycle progression Carranca et al., 1988). Four E2 binding sites are located and cell death follow distinct pathways involving two in the LCR, two of which lie within the promoter, tightly different functions of p53.flanked 5Ј by the Sp1 and 3Ј by the TATA motifs. Keywords: apoptosis/cell cycle/HPV18 E2/p53/ The HPV18 promoter has been shown to be strongly transcription repressed by the BPV-1 E2 and E2TR proteins which presumably hinder the formation of the transcription initiation complex (Thierry and Yaniv, 1987; Dostatni et al., 1991). A moderate repression is also observed with

Human papillomaviruses (HPV) are small DNA viruses that contain a compact and non-redundant genome. HPV, with the help of only few genes, can achieve a complete vegetative cycle specifically in the epidermal and mucosal keratinocytes. Modification of the host cell transcriptional regulation is one of the major ways to regulate the viral production and maturation. The vegetative cycle of papillomaviruses is linked to terminal differentiation of the epithelium and is dependent on the host cell regulatory networks for transcriptional control. The mucosal high risk HPV16 and HPV18 types have been the main models to explore this transcriptional regulation mainly because they are prevalent in cervical cancer as the best studied virally induced cancers in human. In addition, the availability of cell lines, grown from cervical cancers containing integrated HPV16 or 18, represent versatile in vitro models for transcription studies. We will describe here some aspects of the transcriptional regulation that contribute to cell specificity, the basis of which is not yet fully understood despite efforts of numerous groups during the past two decades. Another specificity of small DNA viruses is the multifunctional characteristics of their regulatory proteins due to extreme genomic constraint. We will describe the role played by the viral E2 proteins in the transcriptional repression of the high risk HPV oncogenes and its implication in cervical cancer.