Telomerase-dependent cell cycle regulation requires NOL1 and TINF2 mRNA degradation by HuR modulates telomere function

Abstract

Telomerase is a ribonucleoprotein enzyme that plays a critical role in the maintenance of telomere repeats in most eukaryotic organisms. Although overexpression of telomerase in normal human somatic cells is sufficient to overcome replicative senescence and extend a lifespan, the ability of telomerase to promote tumorigenesis could require additional activities that are independent of its role in telomere extension. Here we identify NOL1 (proliferation-associated nuclear antigen 120) as a TERC-binding protein, which is found in association with catalytically active telomerase. We show that NOL1 binds to cyclin D1 promoter at the TCF binding element and activates its transcription. Moreover, telomerase further enhances expression of cyclin D1 gene by interacting with NOL1 and recruitment to the cyclin D1 promoter, demonstrating a role of telomerase as a modulator of NOL1-dependent transcription in human cancer cells. These data suggest that NOL1 could represent a novel mechanism by which telomerase promotes the prolonged expression of growth-promoting genes critical for the maintenance of tumor survival and cell proliferation. (Chi and Delgado-Olguin 2013)

These data suggest that a functional interplay between NOL1 and telomerase plays a critical role in bypassing checkpoint signaling pathways and maintaining cell proliferation capacity, essential properties of telomerase required for cancer progression.