'Paleontological Institute at The University of Kansas'
Abstract
Regulatory interactions that occur between Polo-like kinase 1 (Plk1) and its protein partners are critical for promoting many different cell division events. Indeed, Plk1 is found mis-regulated in a diverse set of human cancers and has been clinically validated as a drug target in cancer. Here, we use Drosophila as a model to understand how a 217 amino acid protein called Matrimony (Mtrm) regulates the Drosophila homolog of Plk1, Polo kinase, during female meiosis. By analyzing the functionality of a variety of Mtrm mutants, we find that Mtrm and Polo appear to engage in a non-canonical mechanism of interaction in vivo relative to previously described Polo protein interactors. Furthermore, we have identified a Mtrm mutant that separates function during meiosis, suggesting that Mtrm may differentially interact with Polo kinase by at least two different pathways or mechanisms. Thus, in addition to furthering our understanding of the role of Mtrm as a regulator of Polo in Drosophila female meiosis, these studies address a larger, more fundamental question of how Polo interacts with its protein partners in vivo. Elucidating such non-canonical mechanisms of Polo regulation in vivo may contribute to the development of novel and innovative strategies for selective Plk1 inhibition in cancer
