Transcriptional regulation of the papillomavirus oncogenes by cellular and viral transcription factors in cervical carcinoma.
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.
Thierry
Françoise
F
Institute of Medical Biology, Singapore, Singapore. francoise.thierry@imb.a-star.edu.sg
D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000821:virology*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000821:virology*
D009856:Oncogene Proteins, Viral; D014157:Transcription Factors