Advertisement

 

 

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

TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter.
Author Information (click to view)

Rajagopalan D, Pandey AK, Xiuzhen MC, Lee KK, Hora S, Zhang Y, Chua BH, Kwok HS, Bhatia SS, Deng LW, Tenen DG, Kappei D, Jha S,


Rajagopalan D, Pandey AK, Xiuzhen MC, Lee KK, Hora S, Zhang Y, Chua BH, Kwok HS, Bhatia SS, Deng LW, Tenen DG, Kappei D, Jha S, (click to view)

Rajagopalan D, Pandey AK, Xiuzhen MC, Lee KK, Hora S, Zhang Y, Chua BH, Kwok HS, Bhatia SS, Deng LW, Tenen DG, Kappei D, Jha S,

Advertisement

PLoS pathogens 2017 10 1813(10) e1006681 doi 10.1371/journal.ppat.1006681

Abstract

HIV1-TAT interacting 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.

Submit a Comment

Your email address will not be published. Required fields are marked *

eleven − eight =

[ HIDE/SHOW ]