O-GlcNAcylated NF-κB c-Rel is a transcriptional regulator of Acute Myeloid Leukemia

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B895
Abstract ID: 5951

Presenting Author:
Jordan Cress , Graduate Student at Case Western Reserve Univ.

Abstract:

Acute Myeloid Leukemia (AML) is caused by myeloid progenitor cells that undergo malignant transformation which prevents differentiation and induces proliferation. NF-κB transcription factors have been shown to regulate survival, proliferation, and differentiation of AML cells. Around 40% of AML patients exhibit constitutive NF-κB activity which correlates with poor prognosis and increased resistance to chemotherapy. NF-κB proteins are post-translationally modified by O-GlcNAcylation, which control their activity. Protein O-GlcNAcylation is enhanced in AML cells and higher levels of O-GlcNAcylation causes increased NF-κB activity. We have shown that c-Rel is O-GlcNAcylated at S350 in AML and that this modification regulates c-Rel’s ability to bind to specific promoter regions and control transcriptional activation. To study the role of S350 O-GlcNAcylated c-Rel and examine the potential benefit of targeting this specific modification in AML, our lab has developed a novel 4-mer peptoid called OGC350 which specifically targets and blocks the function of S350 O-GlcNAcylated c-Rel.  We show that OGC350 treatment decreases viability of AML cells and suppresses expression of anti-apoptotic genes. Thus far, our data indicates that specific targeting of O-GlcNAcylated c-Rel has therapeutic promise for AML treatment by preventing activation of aberrant c-Rel activity while preserving normal functions of non-O-GlcNAcylated c-Rel.