The human papillomavirus E7 oncoprotein as a regulator of transcription.
High-risk human papillomaviruses (HPVs) encode oncoproteins which manipulate gene expression patterns in the host keratinocytes to facilitate viral replication, regulate viral transcription, and promote immune evasion and persistence. In some cases, oncoprotein-induced changes in host cell behavior can cause progression to cancer, but a complete picture of the functions of the viral oncoproteins in the productive HPV life cycle remains elusive. E7 is the HPV-encoded factor most responsible for maintaining cell cycle competence in differentiating keratinocytes. Through interactions with dozens of host factors, E7 has an enormous impact on host gene expression patterns. In this review, we will examine the role of E7 specifically as a regulator of transcription. We will discuss mechanisms of regulation of cell cycle-related genes by E7 as well as genes involved in immune regulation, growth factor signaling, DNA damage responses, microRNAs, and others pathways. We will also discuss some unanswered questions about how transcriptional regulation by E7 impacts the biology of HPV in both benign and malignant conditions.
Department of Microbiology and Immunology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
William K
WK
Songock
Department of Microbiology and Immunology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
Seong-Man
SM
Kim
Department of Microbiology and Immunology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA. Electronic address: jbodil@lsuhsc.edu.
Jason M
JM
Bodily
D063646:Carcinogenesis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D057131:Immune Evasion; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000276:immunology; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D014158:Transcription, Genetic; D014779:Virus Replication
D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
Cell cycle control; E7; Histone deacetylase; Innate immunity; Transcription factor; pRb family