MOZ and MOZ-CBP cooperate with NF-κB to activate transcription from NF-κB-dependent promoters

Edward M. Chan, Rebecca J. Chan, Elisha M. Comer, Robert J. Goulet, Colin D. Crean, Zachary D. Brown, Amy M. Fruehwald, Zhenyun Yang, H. Scott Boswell, Harikrishna Nakshatri, Theodore G. Gabig

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Objective: Monocytic zinc finger (MOZ) maintains hematopoietic stem cells and, upon fusion to the coactivator CREB-binding protein (CBP), induces acute myeloid leukemia (AML). Leukemic stem cells in AML often exhibit excessive signal-dependent activity of the transcription factor nuclear factor (NF)-κB. Because aberrant interaction between NF-κB and coactivators represents an alternative mechanism for enhancing NF-κB activity, we evaluated whether MOZ and MOZ-CBP cooperate with NF-κB to activate transcription from NF-κB-dependent promoters. Methods: The ability of MOZ, MOZ mutants, and MOZ-CBP to enhance expression of NF-κB-dependent promoters was tested in reporter studies. The interaction between MOZ and NF-κB was evaluated by both coimmunoprecipitation and glutathione S-transferase pulldown assays. Results: MOZ activates transcription from the NF-κB-dependent interleukin-8 promoter; interestingly, this effect is markedly enhanced by CBP. Although MOZ has less potent transcriptional activity than MOZ-CBP, both proteins cooperate with steroid receptor coactivator-1 to activate transcription. MOZ also induces multiple NF-κB-dependent viral promoters. Importantly, MOZ associates in a protein complex with the p65 subunit of NF-κB and interacts directly with p65 in vitro. Transcriptional activity of MOZ requires its C-terminal domain, which is absent from MOZ-CBP, indicating that the transcriptional activity of MOZ-CBP derives from its CBP sequence. Conclusions: MOZ interacts with the p65 subunit of NF-κB and enhances expression of NF-κB-dependent promoters. The more potent transcriptional activity of MOZ-CBP derives from its CBP sequence. Thus, interaction between NF-κB and MOZ-CBP may play an important role in the pathogenesis of certain acute myeloid leukemias.

Original languageEnglish (US)
Pages (from-to)1782-1792
Number of pages11
JournalExperimental Hematology
Volume35
Issue number12
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Chan, E. M., Chan, R. J., Comer, E. M., Goulet, R. J., Crean, C. D., Brown, Z. D., Fruehwald, A. M., Yang, Z., Boswell, H. S., Nakshatri, H., & Gabig, T. G. (2007). MOZ and MOZ-CBP cooperate with NF-κB to activate transcription from NF-κB-dependent promoters. Experimental Hematology, 35(12), 1782-1792. https://doi.org/10.1016/j.exphem.2007.07.015