NOL1 Modulates Cyclin D1 Transcription in Concert with TERT

Telomerase is a unique ribonucleoprotein enzyme which is required for the maintenance of telomere repeats in most eukaryotic organisms. Although overexpression of telomerase in normal human somatic cells is sufficient to overcome replicative senescence, the ability of telomerase to promote tumorigenesis requires 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 TCF binding element of the cyclin D1 promoter and activates its transcription. Telomerase is also recruited to the cyclin D1 promoter through the interaction with NOL1 in a TERC-dependent manner, further enhancing transcription of cyclin D1 gene. These data suggest that a functional interplay between NOL1 and telomerase plays a critical role in maintaining cell proliferation capacity, an essential property of telomerase required for cancer progression.