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Journal Article
Research Support, Non-U.S. Gov't
GRIM-19 Restores Cervical Cancer Cell Senescence by Repressing hTERT Transcription.
Journal of Interferon & Cytokine Research 2016 August
High telomerase activity promotes tumor growth by stabilizing damaged chromosomes and their mitotic replication. Overactivation of telomerase activity has been reported in cervical cancer, a malignancy caused by high-risk human papillomaviruses (HR-HPVs). The HR-HPV E6 can activate hTERT promoter by interacting with E6AP or other binding proteins and by stabilizing the interaction between hTERT and E6AP. GRIM-19 is a novel tumor suppressor that affects multiple targets in a cell to regulate growth. We have previously reported the interaction of GRIM-19 with 18E6 and E6AP to disrupt the E6/E6AP complex and increase the autoubiquitination of E6AP. In this study, we characterized the interaction of GRIM-19 with 16E6 (an oncoprotein produced by HPV16) and identified the binding sites that mediate this interaction. We also found that GRIM-19 expression in cervical cancer cells could inhibit telomerase activity by inhibiting the transactivation of the hTERT promoter by E6, thereby promoting cervical cancer cell senescence. Moreover, we identified a negative correlation between GRIM-19 and hTERT expression in cervical cancer tissues. Suppression of GRIM-19 and induction of hTERT levels were associated with lymph node metastasis, advanced clinical stage, and poor prognosis. This study identified another important novel antitumor molecular link associated with GRIM-19 in the tumorigenesis.
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