Telomerase activates transcription of cyclin D1 gene through an interaction with NOL1.
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 proliferation-associated 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.
['Hong|Juyeong|J|', 'Lee|Ji Hoon|JH|', 'Chung|In Kwon|IK|']
D063646:Carcinogenesis D059447:Cell Cycle Checkpoints D049109:Cell Proliferation D016922:Cellular Senescence D019938:Cyclin D1 D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D009687:Nuclear Proteins D011401:Promoter Regions, Genetic D011485:Protein Binding D012313:RNA D034741:RNA, Small Interfering D051820:TCF Transcription Factors D019098:Telomerase D015533:Transcriptional Activation D012359:tRNA Methyltransferases
Telomerase Cyclin D1 NOL1 Transcriptional activation Tumor cell marker