title: Two different HPV-11E6 fusion proteins trap p53 in the cytoplasm and induce apoptosis.
abstract: Mucosal high risk human papillomaviruses (HPVs) have been shown to be the major cause of cervical cancer. However, the reason why the low risk HPVs only cause proliferative but non-invasive lesions of infected epithelia remains elusive. Because p53 interacts with high risk HPVs E6 and plays a very important role in carcinogenesis, it is assumed that low risk HPVs E6 might interact with p53 in a different pattern. We used mammalian green fluorescent protein (GFP) tagged and polyhistidine (His) tagged proteins expression systems to express HPV-11E6 fusion proteins in wild-type (wt)p53 cell lines, such as 293T and MCF-7 cells to trace the traffic and location of E6s and p53. We showed that: (1) Following transfection, HPV-11E6 was predominantly expressed in the cytoplasm; (2)Using immunocytochemistry and Western blotting, endogenous wt p53 was shown to be trapped in cytoplasm by HPV-11E6 expression. (3) Apoptosis was increased in HPV-11E6 expressed cells. In conclusion, the entrapment of endogenous wt p53 in cytoplasm by the low risk HPV-11E6 may be one of the reasons why low risk HPV is not able to induce malignant transformation.
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Tusheng
authors.initials: T
authors.lastname: Song
authors.forename: Lusheng
authors.initials: L
authors.lastname: Si
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003593:Cytoplasm / Q000502:physiology / Q000821:virology; D005260:Female; D017930:Genes, Reporter; D052163:Human papillomavirus 6 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins