Telomerase activates transcription of cyclin D1 gene through an interaction with NOL1

Abstract

Telomerase is a ribonucleoprotein enzyme that 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 proliferationassociated nucleolar antigen 120 (NOL1, also known as NOP2) as a telomerase RNA component (TERC)-binding protein that 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 remained unclear. We show that NOL1 binds to the T-cell factor (TCF)-binding element of the cyclin D1 promoter and activates its transcription. Interestingly, telomerase is also recruited to the cyclin D1 promoter in a TERC-dependent manner through the interaction with NOL1, further enhancing transcription of the cyclin D1 gene. Depletion of NOL1 suppresses cyclin D1 promoter activity, thereby leading to induction of growth arrest and altered cell cycle distributions. Collectively, our findings suggest that NOL1 represents a new route by which telomerase activates transcription of cyclin D1 gene, thus maintaining cell proliferation capacity.

Plasticity, pleiotropy and fitness trade‐offs in Arabidopsis genotypes with different telomere lengths

“…Both mechanisms are supported by the available literature. Human NOP2 and TERT have nontelomere functions in cell cycle control through direct transcriptional activation of G1 phase cyclin D1 expression (Hong et al ., 2016). Similarly, the direct pleiotropic effects of mutations in Dyskerin and NOP10, which function in telomere biology and ribosomal RNA maturation, could account for the remarkable similarities in human telomere disorders and diseases of ribosome biogenesis (Orsolic et al ., 2016).…”

The Telomerase and Alternative Lengthening of Telomeres Mechanisms Regulate Laryngeal Cancer Cell Apoptosis via the PI3K/Akt Pathway

“…TERT can greatly increase the proliferation capacity of somatic cells [28], and proliferation is a well-known PI3K/Akt pathway-dependent process. Another possible mechanism by which TERT influences the PI3K/Akt pathway is cyclin D1-related cell signaling [29]. Silencing TERT may thus result in the inhibition of the PI3K/Akt pathway.…”