title: Human papillomavirus type 16 E6 inhibits p21(WAF1) transcription independently of p53 by inactivating p150(Sal2).
abstract: HPV16 E6 deregulates G1/S cell cycle progression through p53 degradation preventing transcription of the CDK inhibitor p21(WAF1). However, additional mechanisms independent of p53 inactivation appear to exist. Here, we report that HPV16 E6 targets the cellular factor p150(Sal2), which positively regulates p21(WAF1) transcription. HPV16 E6 associates with p150(Sal2), inducing its functional inhibition by preventing its binding to cis elements on the p21(WAF1) promoter. A HPV16 E6 mutant, L110Q, which was unable to bind p150(Sal2), did not affect the ability of the cellular protein to bind p21(WAF1) promoter, underlining the linkage between these events. These data describe a novel mechanism by which HPV16 E6 induces cell cycle deregulation with a p53-independent pathway. The viral oncoprotein targets p150(Sal2), a positive transcription regulator of p21(WAF1) gene, preventing G1/S arrest and allowing cellular proliferation and efficient viral DNA replication.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Parroche
authors.forename: Majid
authors.initials: M
authors.lastname: Touka
authors.forename: Mariam
authors.initials: M
authors.lastname: Mansour
authors.forename: Véronique
authors.initials: V
authors.lastname: Bouvard
authors.forename: Amélie
authors.initials: A
authors.lastname: Thépot
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.forename: Christine
authors.initials: C
authors.lastname: Carreira
authors.forename: Guillaume G
authors.initials: GG
authors.lastname: Roblot
authors.forename: Bakary S
authors.initials: BS
authors.lastname: Sylla
authors.forename: Uzma
authors.initials: U
authors.lastname: Hasan
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D002453:Cell Cycle; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors*; D004268:DNA-Binding Proteins; D054884:Host-Pathogen Interactions; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D050505:Mutant Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C104147:SALL2 protein, human; D014157:Transcription Factors