Two different HPV-11E6 fusion proteins trap p53 in the cytoplasm and induce apoptosis.
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.
Sun
Lina
L
Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Zhang
Ge
G
Lei
Ting
T
Huang
Chen
C
Song
Tusheng
T
Si
Lusheng
L
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*
D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins