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

Juyeong Hong, Ji Hoon Lee, In Kwon Chung

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22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1566-1579
Number of pages14
JournalJournal of cell science
Issue number8
Publication statusPublished - 2016 Apr 1

Bibliographical note

Funding Information:
This work was supported in part by a grant from the National Research Foundation of Korea [grant number NRF-2013M3A9B6076413 to I.K.C.]; and by a Yonsei University internal grant [grant number 2014-22-0096 to I.K.C.].

Publisher Copyright:
© 2016. Published by The Company of Biologists Ltd.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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