RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth

Oncotarget
Yu QinTaihua Wu

Abstract

hTERT is the key component of telomerase and its overactivation contributes to maintaining telomere length and cell immortalization. Previously, we identified RFPL3 as a new transcription activator of hTERT in lung cancers. However, the exact mechanism of RFPL3 in mediating hTERT activation and its associated signal regulatory network remain unclear. In this study, we found that RFPL3 colocalized and interacted directly with CBP in the nucleus of lung cancer cells. Immunohistochemical analysis of tissue microarrays of lung cancers revealed the simultaneous overexpression of both RFPL3 and CBP predicted relatively poor prognosis. Furthermore, we confirmed their synergistic stimulation on hTERT expression and tumor cell growth. The binding of RFPL3 to hTERT promoter was reduced markedly when CBP was knocked down by its specific siRNA or suppressed by its inhibitor in lung cancer cells with stable overexpression of RFPL3. When one of the two proteins RFPL3 and CBP was upregulated or downregulated, whereas the another remains unchanged, hTERT expression and telomerase activity were activated or repressed accordingly. In the meantime, the growth of lung cancer cells was also promoted or attenuated accordingly. Furthermore, we also f...Continue Reading

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Citations

Aug 8, 2020·Journal of Radiation Research·Guangsheng ZhaiChuanzhao Li
Jul 21, 2017·Cell Death & Disease·Changlin ZhangWuguo Deng
Jan 6, 2021·Cell Chemical Biology·Raghu VannamChristopher J Ott
Jan 26, 2016·Pharmacology & Therapeutics·Stephanie KaypeeTapas K Kundu

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Methods Mentioned

BETA
xenograft
immunoprecipitation assay
acetylation
immunoprecipitation
confocal microscopy
pulldown
electrophoresis
Co-immunoprecipitation
transfection
PCR

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