박진경 전한울 신상철 송치만 이효민 김낙균 김은경 Hwang, Kwang Yeon Lee, Bong-Jin 이인균 2024-01-12T02:30:32Z 2024-01-12T02:30:32Z 2023-05-18 2023-04 https://pubs.kist.re.kr/handle/201004/75742 Aurora kinase A (AURKA) performs critical functions in mitosis. Thus, the activity and subcellular localization of AURKA are tightly regulated and depend on diverse factors including interactions with the multiple binding cofactors. How these different cofactors regulate AURKA to elicit different levels of activity at distinct subcellular locations and times is poorly understood. Here, we identified a conserved region of CEP192, the major cofactor of AURKA, that mediates the interaction with AURKA. Quantitative binding studies were performed to map the interactions of a conserved helix (Helix-1) within CEP192. The crystal structure of Helix-1 bound to AURKA revealed a distinct binding site that is different from other cofactor proteins such as TPX2. Inhibiting the interaction between Helix-1 and AURKA in cells led to the mitotic defects, demonstrating the importance of the interaction. Collectively, we revealed a structural basis for the CEP192-mediated AURKA regulation at the centrosome, which is distinct from TPX2-mediated regulation on the spindle microtubule. English American Association for the Advancement of Science Structural basis for CEP192-mediated regulation of centrosomal AURKA Article 10.1126/sciadv.adf8582 1 Science Advances, v.9, no.16 Science Advances 9 16 Y scie scopus 000983175800008 Multidisciplinary Sciences Science & Technology - Other Topics Article AURORA-A KINASE SPINDLE FORMATION PROTEIN ACTIVATION TPX2 PHOSPHORYLATION CEP192 INCENP INHIBITORS MECHANISM