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Title: TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter
Authors: Rajagopalan D. 
Pandey A.K. 
Xiuzhen M.C.
Lee K.K. 
Hora S.
Zhang Y.
Chua B.H.
Kwok H.S.
Bhatia S.S.
Deng L.W. 
Tenen D.G. 
Kappei D. 
Jha S. 
Keywords: oncoprotein
telomerase reverse transcriptase
transactivator protein
transactivator protein 60
transcription factor Sp1
unclassified drug
histone acetyltransferase
KAT5 protein, human
Sp1 protein, human
TERT protein, human
transcription factor Sp1
tumor protein
cell immortalization
chromatin immunoprecipitation
colony formation
controlled study
down regulation
enzyme active site
gene overexpression
genetic transfection
growth inhibition
human cell
luciferase assay
mass spectrometry
molecular biology
promoter region
protein expression
real time polymerase chain reaction
RNA isolation
site directed mutagenesis
telomeric repeat amplification protocol
transient transfection
uterine cervix cancer
virus infection
Wart virus
Western blotting
DNA responsive element
gene expression regulation
HeLa cell line
uterine cervix tumor
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
HeLa Cells
Histone Acetyltransferases
Neoplasm Proteins
Response Elements
Sp1 Transcription Factor
Uterine Cervical Neoplasms
Issue Date: 2017
Publisher: Public Library of Science
Citation: Rajagopalan D., Pandey A.K., Xiuzhen M.C., Lee K.K., Hora S., Zhang Y., Chua B.H., Kwok H.S., Bhatia S.S., Deng L.W., Tenen D.G., Kappei D., Jha S. (2017). TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter. PLoS Pathogens 13 (10) : e1006681. ScholarBank@NUS Repository.
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. © 2017 Rajagopalan et al.
Source Title: PLoS Pathogens
ISSN: 15537366
DOI: 10.1371/journal.ppat.1006681
Appears in Collections:Staff Publications

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