Nucleophosmin Interacts with PIN2/TERF1-interacting Telomerase Inhibitor 1 (PinX1) and Attenuates the PinX1 Inhibition on Telomerase Activity

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.