IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9428.html
   My bibliography  Save this article

Transcriptional repression by the HDAC4–RelB–p52 complex regulates multiple myeloma survival and growth

Author

Listed:
  • Subrahmanya D. Vallabhapurapu

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

  • Sunil K. Noothi

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

  • Derek A. Pullum

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

  • Charles H. Lawrie

    (Biodonostia Research Institute
    University of Oxford)

  • Rachel Pallapati

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

  • Veena Potluri

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

  • Christian Kuntzen

    (Bridgeport Hospital)

  • Sohaib Khan

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

  • David R. Plas

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

  • Robert Z. Orlowski

    (The University of Texas MD Anderson Cancer Center)

  • Marta Chesi

    (Mayo Clinic)

  • W. Michael Kuehl

    (Genetics Branch, Center for Cancer Research, National Cancer Institute)

  • P. Leif Bergsagel

    (Mayo Clinic)

  • Michael Karin

    (Laboratory of Gene Regulation and Signal Transduction, University of California)

  • Sivakumar Vallabhapurapu

    (The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine)

Abstract

Although transcriptional activation by NF-κB is well appreciated, physiological importance of transcriptional repression by NF-κB in cancer has remained elusive. Here we show that an HDAC4–RelB–p52 complex maintains repressive chromatin around proapoptotic genes Bim and BMF and regulates multiple myeloma (MM) survival and growth. Disruption of RelB–HDAC4 complex by a HDAC4-mimetic polypeptide blocks MM growth. RelB-p52 also represses BMF translation by regulating miR-221 expression. While the NIK-dependent activation of RelB-p52 in MM has been reported, we show that regardless of the activation status of NIK and the oncogenic events that cause plasma cell malignancy, several genetically diverse MM cells including Bortezomib-resistant MM cells are addicted to RelB-p52 for survival. Importantly, RelB is constitutively phosphorylated in MM and ERK1 is a RelB kinase. Phospho-RelB remains largely nuclear and is essential for Bim repression. Thus, ERK1-dependent regulation of nuclear RelB is critical for MM survival and explains the NIK-independent role of RelB in MM.

Suggested Citation

  • Subrahmanya D. Vallabhapurapu & Sunil K. Noothi & Derek A. Pullum & Charles H. Lawrie & Rachel Pallapati & Veena Potluri & Christian Kuntzen & Sohaib Khan & David R. Plas & Robert Z. Orlowski & Marta , 2015. "Transcriptional repression by the HDAC4–RelB–p52 complex regulates multiple myeloma survival and growth," Nature Communications, Nature, vol. 6(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9428
    DOI: 10.1038/ncomms9428
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9428
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9428?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
    ---><---

    Citations

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


    Cited by:

    1. Daniel A. Ang & Jean-Michel Carter & Kamalakshi Deka & Joel H. L. Tan & Jianbiao Zhou & Qingfeng Chen & Wee Joo Chng & Nathan Harmston & Yinghui Li, 2024. "Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:6:y:2015:i:1:d:10.1038_ncomms9428. 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.