Author(s): Bokai Zhang,
Mentor(s): Jeffery S. Tessem
Institution BYU
Approximately 11.6% of the U.S. population has been diagnosed with diabetes. Diabetes mellitus is a metabolic disorder characterized by the progressive loss of functional pancreatic β-cell mass. Thus, restoring β-cell mass and function is critical for diabetes treatment. NF-κB canonical signaling cascade regulates the immune and inflammatory responses of cells. This in turn regulates proliferation, cell survival, and apoptosis in β-cells. The transcription factor p65 (RelA) serves as a key component of this signaling cascade, as p65 also affects β- cell dysfunction and apoptosis under hyperglycemia and inflammatory conditions. However, the knockout of the RelA gene impairs insulin secretion and causes glucose intolerance in mice, suggesting that it plays a dual role in regulating functional β-cell mass. While its role in inflammatory signaling and β-cell function has been studied, the mechanism for these effects remains poorly characterized. This research intends to identify and validate p65 binding partners and hypothesize that p65 binding activities are altered under inflammatory stress. Here we present p65 binding partners under normal and inflammatory stress conditions. Understanding the interactions of p65 with its binding partners, in the presence and absence of proinflammatory cytokines, is key to unraveling its mechanisms in β-cell function and survival.