IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15289-7.html
   My bibliography  Save this article

CDK1 dependent phosphorylation of hTERT contributes to cancer progression

Author

Listed:
  • Mami Yasukawa

    (National Cancer Center Research Institute)

  • Yoshinari Ando

    (National Cancer Center Research Institute)

  • Taro Yamashita

    (Kanazawa University Graduate School of Medical Science)

  • Yoko Matsuda

    (Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
    Kagawa University)

  • Shisako Shoji

    (RIKEN Center for Biosystems Dynamics Research)

  • Masaki Suimye Morioka

    (RIKEN Center for Integrative Medical Sciences)

  • Hideya Kawaji

    (RIKEN Center for Integrative Medical Sciences
    RIKEN Preventive Medicine and Diagnosis Innovation Program)

  • Kumiko Shiozawa

    (National Cancer Center Research Institute)

  • Mitsuhiro Machitani

    (National Cancer Center Research Institute)

  • Takaya Abe

    (RIKEN Center for Life Science Technologies
    RIKEN Center for Life Science Technologies)

  • Shinji Yamada

    (Tohoku University Graduate School of Medicine)

  • Mika K. Kaneko

    (Tohoku University Graduate School of Medicine)

  • Yukinari Kato

    (Tohoku University Graduate School of Medicine
    Tohoku University)

  • Yasuhide Furuta

    (RIKEN Center for Life Science Technologies
    RIKEN Center for Life Science Technologies)

  • Tadashi Kondo

    (National Cancer Center Research Institute)

  • Mikako Shirouzu

    (RIKEN Center for Biosystems Dynamics Research)

  • Yoshihide Hayashizaki

    (RIKEN Preventive Medicine and Diagnosis Innovation Program)

  • Shuichi Kaneko

    (Kanazawa University Graduate School of Medical Science)

  • Kenkichi Masutomi

    (National Cancer Center Research Institute)

Abstract

The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses reveal that phosphorylation of hTERT at threonine 249 occurs more frequently in aggressive cancers. Using CRISPR/Cas9 genome editing, we introduce substitution mutations at threonine 249 in the endogenous hTERT locus and find that phosphorylation of threonine 249 is necessary for hTERT-mediated RNA dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase and terminal transferase activities. Cap Analysis of Gene Expression (CAGE) demonstrates that hTERT phosphorylation at 249 regulates the expression of specific genes that are necessary for cancer cell proliferation and tumor formation. These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner.

Suggested Citation

  • Mami Yasukawa & Yoshinari Ando & Taro Yamashita & Yoko Matsuda & Shisako Shoji & Masaki Suimye Morioka & Hideya Kawaji & Kumiko Shiozawa & Mitsuhiro Machitani & Takaya Abe & Shinji Yamada & Mika K. Ka, 2020. "CDK1 dependent phosphorylation of hTERT contributes to cancer progression," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15289-7
    DOI: 10.1038/s41467-020-15289-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15289-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-15289-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15289-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.