Abstract
Telomerase activation and telomere maintenance are critical for cellular immortalization and transformation. PIN2/TERF1-interacting telomerase inhibitor 1 (PinX1) is a telomerase regulator and the aberrant expression of PinX1 causes telomere shortening. Identifying PinX1-interacting proteins is important for understanding telomere maintenance. We found that PinX1 directly interacts with nucleophosmin (NPM), a protein that has been shown to positively correlate with telomerase activity. We further showed that PinX1 acts as a linker in the association between NPM and hTERT, the catalytic subunit of telomerase. Additionally, the recruitment of NPM by PinX1 to the telomerase complex could partially attenuate the PinX1-mediated inhibition on telomerase activity. Taken together, our data reveal a novel mechanism that regulates telomerase activation through the interaction between NPM, PinX1 and the telomerase complex.
Highlights
PinX1 can directly interact with hTERT and hTR13
We have shown that NPM interacts directly with PinX1 and forms a complex with hTERT, the catalytic subunit of telomerase (Figs 1 and 2)
The recruitment of NPM by PinX1 to telomerase can attenuate the inhibitory effect of PinX1 on telomerase activity
Summary
PinX1 can directly interact with hTERT and hTR13 This protein is a potent telomerase inhibitor that can suppress telomerase enzymatic activity and shorten the telomeres upon overexpression[14]. PinX1 expression is up-regulated in glioma tissues[15], and it has been revealed that silencing PinX1 enhances telomerase activity and leads to telomere shortening at the same time[16]. We found that the silencing of PinX1 disrupted the recruitment of telomerase to telomeres[18]. That PinX1 is not solely a negative regulator; it may act as a mediator in telomerase recruitment or activation, likely with assistance from some of its interacting partners. The present report provides evidence that NPM interacts with PinX1 directly and reveals a role of the PinX1/ NPM interaction in telomerase regulation
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