Presentation description

Acute Myeloid Leukemia (AML) is a rare and aggressive blood cancer marked by the uncontrolled growth of immature myeloid cells in the bone marrow. One major contributor to AML progression is the PI3K (Phosphoinositide 3-kinase) signaling pathway, which regulates key cell functions such as survival, proliferation, and metabolism. This pathway includes a core complex of two proteins: a regulatory subunit (p85α) and a catalytic subunit (p110α). The balance between these subunits is critical for normal PI3K function, and its disruption can lead to cancer.
Post-translational modifications like phosphorylation and ubiquitination are key regulators of p85α stability and function. The F-box protein FBXO21, part of the SCF E3 ubiquitin ligase complex, has been shown to ubiquitinate p85α, targeting it for degradation. However, it remains unclear how phosphorylation affects this interaction.
To investigate, we performed in vitro ubiquitination assays using wild-type and phosphorylation site-mutant forms of p85α at T454, Y452, Y463, Y467, and Y647. Our results could indicate whether phosphorylation at these sites is requisite for interaction with p85α or FBXO2.
We are also using kinase inhibitors to identify the enzymes responsible for these modifications. These findings may reveal new therapeutic targets in AML by identifying key regulators of PI3K signaling.