한빛사 논문
Jung-Eun Park1, Liang Zhang1, Jeong Kyu Bang2, Thorkell Andresson3, Frank DiMaio4 & Kyung S. Lee1,*
1 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
2 Division of Magnetic Resonance, Korea Basic Science Institute, 162 Yeongudanji-ro, Ochang-eup, Cheongju 28119, Republic of Korea.
3 Protein Characterization Laboratory, Frederick National Laboratory for Cancer Research and Leidos Biomedical Research Inc., 8560 Progress Drive, Frederick, MD 21702, USA.
4 Department of Biochemistry and Institute for Protein Design, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195
*Correspondence to Kyung S. Lee
Abstract
Tight control of centriole duplication is critical for normal chromosome segregation and the maintenance of genomic stability. Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis. How Plk4 dynamically promotes its symmetry-breaking relocalization and achieves its procentriole-assembly state remains unknown. Here we show that Plk4 is a unique kinase that utilizes its autophosphorylated noncatalytic cryptic polo-box (CPB) to phase separate and generate a nanoscale spherical condensate. Analyses of the crystal structure of a phospho-mimicking, condensation-proficient CPB mutant reveal that a disordered loop at the CPB PB2-tip region is critically required for Plk4 to generate condensates and induce procentriole assembly. CPB phosphorylation also promotes Plk4’s dissociation from the Cep152 tether while binding to downstream STIL, thus allowing Plk4 condensate to serve as an assembling body for centriole biogenesis. This study uncovers the mechanism underlying Plk4 activation and may offer strategies for anti-Plk4 intervention against genomic instability and cancer.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기