Aurora Kinase A proximity map reveals centriolar satellites as regulators of its ciliary function

Aurora kinase A (AURKA) is a conserved kinase that plays crucial roles in numerous cellular processes. Although AURKA overexpression is frequent in human cancers, its pleiotropic functions and multifaceted regulation present challenges in its therapeutic targeting. Key to overcoming these challenges is to identify and characterize the full range of AURKA interactors, which are often weak and transient. Previous proteomic studies were limited in monitoring dynamic and non-mitotic AURKA interactions. Here, we generate the proximity interactome of AURKA in asynchronous cells, which consists of 440 proteins involving multiple biological processes and cellular compartments. Importantly, AURKA has extensive proximate and physical interactions to centriolar satellites, key regulators of the primary cilium. Loss-of-function experiments identify satellites as negative regulators of AURKA activity, abundance, and localization in quiescent cells. Notably, loss of satellites activates AURKA at the basal body, decreases centrosomal IFT88 levels, and causes ciliogenesis defects. Collectively, our results provide a resource for dissecting spatiotemporal regulation of AURKA and uncover its proteostatic regulation by satellites as a new mechanism for its ciliary functions. SYNOPSIS This study presents the in vivo proximity interactome of AURKA in asynchronous cells, which reveals a new regulatory and functional relationship between AURKA and centriolar satellites. AURKA proximity interactome is composed of 440 proteins involving diverse biological processes and cellular compartments. AURKA has extensive interactions with centriolar satellite proteins. Depletion of centriolar satellites increases cellular and centrosomal abundance and activation of AURKA. AURKA inhibition rescues the ciliogenesis defects of cells depleted for centriolar satellites. Graphical Abstract This study presents the in vivo proximity interactome of AURKA in asynchronous cells, which reveals a new regulatory and functional relationship between AURKA and centriolar satellites.