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Smurf2 suppresses B-cell proliferation and lymphomagenesis by mediating ubiquitination and degradation of YY1

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  • Charusheila Ramkumar

    (University of Massachusetts Medical School)

  • Hang Cui

    (University of Massachusetts Medical School)

  • Yahui Kong

    (University of Massachusetts Medical School)

  • Stephen N. Jones

    (University of Massachusetts Medical School)

  • Rachel M. Gerstein

    (University of Massachusetts Medical School)

  • Hong Zhang

    (University of Massachusetts Medical School)

Abstract

About half of patients with diffuse large B-cell lymphoma (DLBCL) do not respond to or relapse soon after the standard chemotherapy, indicating a critical need to better understand the specific pathways perturbed in DLBCL for developing effective therapeutic approaches. Mice deficient in the E3 ubiquitin ligase Smurf2 spontaneously develop B-cell lymphomas that resemble human DLBCL with molecular features of germinal centre or post-germinal centre B cells. Here we show that Smurf2 mediates ubiquitination and degradation of YY1, a key germinal centre transcription factor. Smurf2 deficiency enhances YY1-mediated transactivation of c-Myc and B-cell proliferation. Furthermore, Smurf2 expression is significantly decreased in primary human DLBCL samples, and low levels of Smurf2 expression correlate with inferior survival in DLBCL patients. The Smurf2-YY1-c-Myc regulatory axis represents a novel pathway perturbed in DLBCL that suppresses B-cell proliferation and lymphomagenesis, suggesting pharmaceutical targeting of Smurf2 as a new therapeutic paradigm for DLBCL.

Suggested Citation

  • Charusheila Ramkumar & Hang Cui & Yahui Kong & Stephen N. Jones & Rachel M. Gerstein & Hong Zhang, 2013. "Smurf2 suppresses B-cell proliferation and lymphomagenesis by mediating ubiquitination and degradation of YY1," Nature Communications, Nature, vol. 4(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3598
    DOI: 10.1038/ncomms3598
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