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Functional analysis of CDC7 protein which is interacted with HPV E6 / 대한산부인과학회지
Korean Journal of Obstetrics and Gynecology ; : 459-464, 2007.
Article in Korean | WPRIM | ID: wpr-41840
ABSTRACT

OBJECTIVE:

Human papillomaviruses are associated with the majority of cervical cancers. There is a wide effort focused on searching for the target of the involvement of p53-independent HPV-16E6 interacting proteins. We identified Cdc7 (cell division cycle 7-related protein kinases) as a binding partner of E6 and investigated its biological function in cervical cancer cells.

METHODS:

The baits, E6, fused to the LexA-BD subunit using pBTM116 vector were used to screen an oligoneucleotide primed human HeLa cDNA library cloned in pGAD10 vector. Yeast two-hybrid screens were performed. Immunoprecipitation assay was performed to determine whether E6-Cdc7 interaction occurred. Cells treated with siRNA were analysed by flow cytometry.

RESULTS:

We have delinated the interactions of E6 with five proteins, namely the IRF-3 (interferon regulatory factor-3), PRKCL?1 (protein kinase C-like 1), PIST (PDZ/coiled-coil domain binding gene), BARD1 (BRCA1 assocated ring domain 1), and Cdc7. The in vitro result of the interaction between E6 and Cdc7 was confirmed by immunoprecipitation experiments. Down-regulation of Cdc7 by small interfering RNA in HeLa cell lines causes an abortive S phase, leading to cell death.

CONCLUSION:

We have identified the new protein of interaction with HPV E6, Cdc7 kinase. It has been implicated in S phase signaling of cell cycle and the inhibition of Cdc7 induced cell death. But, further investigation is needed to know the biologic function of Cdc7 kinase in cervical carcinogenesis.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphotransferases / Yeasts / HeLa Cells / Down-Regulation / Gene Library / Cell Cycle / Uterine Cervical Neoplasms / S Phase / Cell Death / Clone Cells Type of study: Prognostic study Limits: Humans Language: Korean Journal: Korean Journal of Obstetrics and Gynecology Year: 2007 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphotransferases / Yeasts / HeLa Cells / Down-Regulation / Gene Library / Cell Cycle / Uterine Cervical Neoplasms / S Phase / Cell Death / Clone Cells Type of study: Prognostic study Limits: Humans Language: Korean Journal: Korean Journal of Obstetrics and Gynecology Year: 2007 Type: Article