Telomerase activates transcription of cyclin D1 gene through the interaction with NOL1.

Abstract

Telomerase is a ribonucleoprotein enzyme which is required for the maintenance of telomere repeats. 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 nucleolar antigen 120) as a TERC-binding protein, which is found in association with catalytically active telomerase. Although NOL1 is highly expressed in the majority of human tumor cells, the molecular mechanism by which NOL1 contributes to tumorigenesis remains unclear. We show that NOL1 binds to TCF binding element of the cyclin D1 promoter and activates its transcription. Interestingly, 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. Depletion of NOL1 suppresses cyclin D1 promoter activity, thereby leading to induction of growth arrest and altered cell cycle distribution. Collectively, our findings suggest that NOL1 represents a new route by which telomerase activates transcription of cyclin D1 gene, thus maintaining cell proliferation capacity.