IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28265-0.html
   My bibliography  Save this article

Cyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division

Author

Listed:
  • Katharina Clemm von Hohenberg

    (German Cancer Research Center (DKFZ)
    Heidelberg University
    CellNetworks—Cluster of Excellence, Heidelberg University
    Universitätsmedizin Mannheim)

  • Sandra Müller

    (German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Sibylle Schleich

    (German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Matthias Meister

    (German Cancer Research Center (DKFZ))

  • Jonathan Bohlen

    (German Cancer Research Center (DKFZ)
    Heidelberg University
    CellNetworks—Cluster of Excellence, Heidelberg University
    Laboratory of Human Genetics of Infectious Diseases, Necker Branch)

  • Thomas G. Hofmann

    (University Medical Center Mainz at the Johannes Gutenberg University of Mainz)

  • Aurelio A. Teleman

    (German Cancer Research Center (DKFZ)
    Heidelberg University
    CellNetworks—Cluster of Excellence, Heidelberg University)

Abstract

DENR and MCTS1 have been identified as oncogenes in several different tumor entities. The heterodimeric DENR·MCTS1 protein complex promotes translation of mRNAs containing upstream Open Reading Frames (uORFs). We show here that DENR is phosphorylated on Serine 73 by Cyclin B/CDK1 and Cyclin A/CDK2 at the onset of mitosis, and then dephosphorylated as cells exit mitosis. Phosphorylation of Ser73 promotes mitotic stability of DENR protein and prevents its cleavage at Asp26. This leads to enhanced translation of mRNAs involved in mitosis. Indeed, we find that roughly 40% of all mRNAs with elevated translation in mitosis are DENR targets. In the absence of DENR or of Ser73 phosphorylation, cells display elevated levels of aberrant mitoses and cell death. This provides a mechanism how the cell cycle regulates translation of a subset of mitotically relevant mRNAs during mitosis.

Suggested Citation

  • Katharina Clemm von Hohenberg & Sandra Müller & Sibylle Schleich & Matthias Meister & Jonathan Bohlen & Thomas G. Hofmann & Aurelio A. Teleman, 2022. "Cyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28265-0
    DOI: 10.1038/s41467-022-28265-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28265-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28265-0?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
    ---><---

    References listed on IDEAS

    as
    1. Jonathan Bohlen & Liza Harbrecht & Saioa Blanco & Katharina Clemm von Hohenberg & Kai Fenzl & Günter Kramer & Bernd Bukau & Aurelio A. Teleman, 2020. "DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    2. Sibylle Schleich & Katrin Strassburger & Philipp Christoph Janiesch & Tatyana Koledachkina & Katharine K. Miller & Katharina Haneke & Yong-Sheng Cheng & Katrin Küchler & Georg Stoecklin & Kent E. Dunc, 2014. "DENR–MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth," Nature, Nature, vol. 512(7513), pages 208-212, August.
    3. Björn Schwanhäusser & Dorothea Busse & Na Li & Gunnar Dittmar & Johannes Schuchhardt & Jana Wolf & Wei Chen & Matthias Selbach, 2011. "Global quantification of mammalian gene expression control," Nature, Nature, vol. 473(7347), pages 337-342, May.
    4. Deepika Vasudevan & Sarah D. Neuman & Amy Yang & Lea Lough & Brian Brown & Arash Bashirullah & Timothy Cardozo & Hyung Don Ryoo, 2020. "Translational induction of ATF4 during integrated stress response requires noncanonical initiation factors eIF2D and DENR," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Athena Kyrkou & Robert Valla & Yao Zhang & Giulia Ambrosi & Stephanie Laier & Karin Müller-Decker & Michael Boutros & Aurelio A. Teleman, 2024. "G6PD and ACSL3 are synthetic lethal partners of NF2 in Schwann cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ramona Weber & Leon Kleemann & Insa Hirschberg & Min-Yi Chung & Eugene Valkov & Cátia Igreja, 2022. "DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5′ leaders," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Baiwen Chen & Jiajia Hu & Xianting Hu & Huifang Chen & Rujuan Bao & Yatao Zhou & Youqiong Ye & Meixiao Zhan & Wei Cai & Huabin Li & Hua-Bing Li, 2022. "DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Yuping Chen & Jo-Hsi Huang & Connie Phong & James E. Ferrell, 2024. "Viscosity-dependent control of protein synthesis and degradation," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Gábor Csárdi & Alexander Franks & David S Choi & Edoardo M Airoldi & D Allan Drummond, 2015. "Accounting for Experimental Noise Reveals That mRNA Levels, Amplified by Post-Transcriptional Processes, Largely Determine Steady-State Protein Levels in Yeast," PLOS Genetics, Public Library of Science, vol. 11(5), pages 1-32, May.
    5. Ying Xue & Fujia Lu & Zhenzhen Chang & Jing Li & Yuan Gao & Jie Zhou & Ying Luo & Yongfeng Lai & Siyuan Cao & Xiaoxiao Li & Yuhan Zhou & Yan Li & Zheng Tan & Xiang Cheng & Xiong Li & Jing Chen & Weimi, 2023. "Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. Kaslik, Eva & Rădulescu, Ileana Rodica, 2022. "Stability and bifurcations in fractional-order gene regulatory networks," Applied Mathematics and Computation, Elsevier, vol. 421(C).
    7. Suran Kim & Sungjin Min & Yi Sun Choi & Sung-Hyun Jo & Jae Hun Jung & Kyusun Han & Jin Kim & Soohwan An & Yong Woo Ji & Yun-Gon Kim & Seung-Woo Cho, 2022. "Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    8. Lingling Li & Dongxian Jiang & Qiao Zhang & Hui Liu & Fujiang Xu & Chunmei Guo & Zhaoyu Qin & Haixing Wang & Jinwen Feng & Yang Liu & Weijie Chen & Xue Zhang & Lin Bai & Sha Tian & Subei Tan & Chen Xu, 2023. "Integrative proteogenomic characterization of early esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    9. Thomas C. J. Tan & Van Kelly & Xiaoyan Zou & David Wright & Tony Ly & Rose Zamoyska, 2022. "Translation factor eIF5a is essential for IFNγ production and cell cycle regulation in primary CD8+ T lymphocytes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Jonathan J. Swietlik & Stefanie Bärthel & Chiara Falcomatà & Diana Fink & Ankit Sinha & Jingyuan Cheng & Stefan Ebner & Peter Landgraf & Daniela C. Dieterich & Henrik Daub & Dieter Saur & Felix Meissn, 2023. "Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Ryosuke Ishimura & Afnan H. El-Gowily & Daisuke Noshiro & Satoko Komatsu-Hirota & Yasuko Ono & Mayumi Shindo & Tomohisa Hatta & Manabu Abe & Takefumi Uemura & Hyeon-Cheol Lee-Okada & Tarek M. Mohamed , 2022. "The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Sébastien Durand & Marion Bruelle & Fleur Bourdelais & Bigitha Bennychen & Juliana Blin-Gonthier & Caroline Isaac & Aurélia Huyghe & Sylvie Martel & Antoine Seyve & Christophe Vanbelle & Annie Adrait , 2023. "RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Rune B Jakobsen & Esben Østrup & Xiaolan Zhang & Tarjei S Mikkelsen & Jan E Brinchmann, 2014. "Analysis of the Effects of Five Factors Relevant to In Vitro Chondrogenesis of Human Mesenchymal Stem Cells Using Factorial Design and High Throughput mRNA-Profiling," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-13, May.
    14. Beatrice T. Laudenbach & Karsten Krey & Quirin Emslander & Line Lykke Andersen & Alexander Reim & Pietro Scaturro & Sarah Mundigl & Christopher Dächert & Katrin Manske & Markus Moser & Janos Ludwig & , 2021. "NUDT2 initiates viral RNA degradation by removal of 5′-phosphates," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    15. McNutt Patrick & Gut Ian & Hubbard Kyle & Beske Phil, 2015. "A novel method to prioritize RNAseq data for post-hoc analysis based on absolute changes in transcript abundance," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 14(3), pages 227-241, June.
    16. Elena Grahn & Svenja V. Kaufmann & Malika Askarova & Momchil Ninov & Luisa M. Welp & Thomas K. Berger & Henning Urlaub & U.Benjamin Kaupp, 2023. "Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    17. Kaushik Bhattacharya & Samarpan Maiti & Szabolcs Zahoran & Lorenz Weidenauer & Dina Hany & Diana Wider & Lilia Bernasconi & Manfredo Quadroni & Martine Collart & Didier Picard, 2022. "Translational reprogramming in response to accumulating stressors ensures critical threshold levels of Hsp90 for mammalian life," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    18. Erik. T. Frank & Lucie Kesner & Joanito Liberti & Quentin Helleu & Adria C. LeBoeuf & Andrei Dascalu & Douglas B. Sponsler & Fumika Azuma & Evan P. Economo & Patrice Waridel & Philipp Engel & Thomas S, 2023. "Targeted treatment of injured nestmates with antimicrobial compounds in an ant society," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    19. Marzieh Marzbany & Fatemeh Ghassemi & Mahsa Rasekhian, 2019. "Application of the 3'-Untranslated Region of Messenger RNA from Measles Virus Matrix Protein as an RNA Stabilizer: Implications in Pharmaceutical Biotechnology," Journal of Molecular Biology Research, Canadian Center of Science and Education, vol. 9(1), pages 1-53, December.
    20. Omar M. Hedaya & Kadiam C. Venkata Subbaiah & Feng Jiang & Li Huitong Xie & Jiangbin Wu & Eng-Soon Khor & Mingyi Zhu & David H. Mathews & Chris Proschel & Peng Yao, 2023. "Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    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:13:y:2022:i:1:d:10.1038_s41467-022-28265-0. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.