Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/79473
Title: c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells
Authors: Lim, Jun Feng
Grumont, Raelene
Gerondakis, Steve
Su, I-hsin
Neo, Wen Hao
Keywords: DRNTU::Science::Biological sciences::Biochemistry
Issue Date: 2014
Source: Neo, W. H., Lim, J. F., Grumont, R., Gerondakis, S., & Su, I.-h. (2014). c-rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells. Journal of biological chemistry, 289(46), 31693-31707.
Series/Report no.: Journal of biological chemistry
Abstract: The polycomb group protein Ezh2 is a histone methyltransferase that modifies chromatin structure to alter gene expression during embryonic development, lymphocyte activation, and tumorigenesis. The mechanism by which Ezh2 expression is regulated is not well defined. In the current study, we report that c-Rel is a critical activator of Ezh2 transcription in lymphoid cells. In activated primary murine B and T cells, plus human leukemia and multiple myeloma cell lines, recruitment of c-Rel to the first intron of the Ezh2 locus promoted Ezh2 mRNA expression. This up-regulation was abolished in activated c-Rel-deficient lymphocytes and by c-Rel knockdown in Jurkat T cells. Treatment of malignant cells with the c-Rel inhibitor pentoxifylline not only reduced c-Rel nuclear translocation and Ezh2 expression, but also enhanced their sensitivity to the Ezh2-specific drug, GSK126 through increased growth inhibition and cell death. In summary, our demonstration that c-Rel regulates Ezh2 expression in lymphocytes and malignant lymphoid cells reveals a novel transcriptional network in transformed lymphoid cells expressing high levels of Ezh2 that provides a molecular justification for combinatorial drug therapy.
URI: https://hdl.handle.net/10356/79473
http://hdl.handle.net/10220/25127
DOI: 10.1074/jbc.M114.574517
Rights: © 2014 American Society for Biochemistry and Molecular Biology. This is the author created version of a work that has been peer reviewed and accepted for publication by The Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [Article URL/DOI: http://dx.doi.org/10.1074/jbc.M114.574517].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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