Structural basis for CEP192-mediated regulation of centrosomal AURKA

Jin Gyeong Park, Hanul Jeon, Sangchul Shin, Chiman Song, Hyomin Lee, Nak Kyoon Kim, Eunice Eun Kyeong Kim, Kwang Yeon Hwang, Bong Jin Lee, In Gyun Lee

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1 Citation (Scopus)


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.

Original languageEnglish
Article numbereadf8582
JournalScience Advances
Issue number16
Publication statusPublished - 2023 Apr

Bibliographical note

Funding Information:
Acknowledgments:W ethankHakSukChungforhelpwithx-raydiffra ction datacollectionand analysis.W ealsothankbeamlinestaffatthePohangAcceleratorLaboratory(BeamlineBL-5C, BL-7A,andBL-11C)forassistancewiththex-ra ydiffractionexperiments.Funding:Thiswork was supported by the research support program of the Lim Sung Ki Foundation (LF-RSP2022-02),bytheintramuralgrantsofKoreaInstituteofScienceandT echnology (KIST ,no.2E32333 and2V09702),andbytheNationalresearchcouncilofScienceandT echnology (NST)grantfrom theKoreangovernment(MSIT ,no.CPS21061-100).Authorcontributions:I.-G.L.conceivedand ledthestudy.J.-G.P .andI.-G.L.designedandperformedthebiochemical,structural,andcellular experiments.H.J.purifiedtheproteins.S.S.collectedandanalyzedthex-ra ydiffra ction data.C.S. andH.L.performedthecellularexperimentsandprovidedtechnicalexpertise.K.Y .H., E.E.K.,and B.-J.L.curatedandanalyzedthedata.N.-K.K.performedmultianglelightscattering.J.-G.P .and I.-G.L.wrotethemanuscript.Competinginterests:Theauthorsdeclarethattheyhaveno competinginterests.Dataandmaterialsavailability:Atomiccoordinatesandstructure factorsforthestructureofCEP192-AURKAchimeraweredepositedwiththeProteinDataBank (PDB)underaccessioncode8GUW .Alldataneededtoevaluatetheconclusionsinthepaperare presentinthepaperand/ortheSupplementaryMaterials.

Funding Information:
This work was supported by the research support program of the Lim Sung Ki Foundation (LF-RSP2022-02), by the intramural grants of Korea Institute of Science and Technology (KIST, no. 2E32333 and 2V09702), and by the National research council of Science and Technology (NST) grant from the Korean government (MSIT, no. CPS21061-100).

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Copyright © 2023 The Authors, some rights reserved.

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