TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter

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TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter

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Title: TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter
Author: Rajagopalan, Deepa; Pandey, Amit Kumar; Xiuzhen, Magdalene Claire; Lee, Kwok Kin; Hora, Shainan; Zhang, Yanzhou; Chua, Boon Haow; Kwok, Hui Si; Bhatia, Shreshtha Sailesh; Deng, Lih Wen; Tenen, Daniel G.; Kappei, Dennis; Jha, Sudhakar

Note: Order does not necessarily reflect citation order of authors.

Citation: Rajagopalan, D., A. K. Pandey, M. C. Xiuzhen, K. K. Lee, S. Hora, Y. Zhang, B. H. Chua, et al. 2017. “TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter.” PLoS Pathogens 13 (10): e1006681. doi:10.1371/journal.ppat.1006681. http://dx.doi.org/10.1371/journal.ppat.1006681.
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Abstract: HIV1-TAT interactive protein (TIP60) is a haploinsufficient tumor suppressor. However, the potential mechanisms endowing its tumor suppressor ability remain incompletely understood. It plays a vital role in virus-induced cancers where TIP60 down-regulates the expression of human papillomavirus (HPV) oncoprotein E6 which in turn destabilizes TIP60. This intrigued us to identify the role of TIP60, in the context of a viral infection, where it is targeted by oncoproteins. Through an array of molecular biology techniques such as Chromatin immunoprecipitation, expression analysis and mass spectrometry, we establish the hitherto unknown role of TIP60 in repressing the expression of the catalytic subunit of the human telomerase complex, TERT, a key driver for immortalization. TIP60 acetylates Sp1 at K639, thus inhibiting Sp1 binding to the TERT promoter. We identified that TIP60-mediated growth suppression of HPV-induced cervical cancer is mediated in part due to TERT repression through Sp1 acetylation. In summary, our study has identified a novel substrate for TIP60 catalytic activity and a unique repressive mechanism acting at the TERT promoter in virus-induced malignancies.
Published Version: doi:10.1371/journal.ppat.1006681
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662243/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493197
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