The Crk4-Cyc4 complex regulates G2/M transition in Toxoplasma gondii

被引:6
|
作者
Hawkins, Lauren M. [1 ]
Wang, Chengqi [2 ]
Chaput, Dale [3 ]
Batra, Mrinalini [1 ]
Marsilia, Clem [1 ]
Awshah, Danya [1 ]
Suvorova, Elena S. [1 ]
机构
[1] Univ S Florida, Morsani Coll Med, Dept Internal Med, Div Infect Dis, Tampa, FL 33612 USA
[2] Univ S Florida, Coll Publ Hlth, Tampa, FL 33612 USA
[3] Univ S Florida, Coll Arts & Sci, Prote Core, Tampa, FL 33612 USA
来源
EMBO JOURNAL | 2024年 / 43卷 / 11期
基金
美国国家卫生研究院;
关键词
Apicomplexa; Toxoplasma gondii; Cell Cycle; CDK; G(2)/M Checkpoint; MULTIPLE SEQUENCE ALIGNMENT; DNA-REPLICATION; CELL-CYCLE; HUMAN CDT1; DIVISION; DESTRUCTION; PROTEOLYSIS; CENTROSOME; PLATFORM; KINASES;
D O I
10.1038/s44318-024-00095-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A versatile division of apicomplexan parasites and a dearth of conserved regulators have hindered the progress of apicomplexan cell cycle studies. While most apicomplexans divide in a multinuclear fashion, Toxoplasma gondii tachyzoites divide in the traditional binary mode. We previously identified five Toxoplasma CDK-related kinases (Crk). Here, we investigated TgCrk4 and its cyclin partner TgCyc4. We demonstrated that TgCrk4 regulates conventional G2 phase processes, such as repression of chromosome rereplication and centrosome reduplication, and acts upstream of the spindle assembly checkpoint. The spatial TgCyc4 dynamics supported the TgCrk4-TgCyc4 complex role in the coordination of chromosome and centrosome cycles. We also identified a dominant TgCrk4-TgCyc4 complex interactor, TgiRD1 protein, related to DNA replication licensing factor CDT1 but played no role in licensing DNA replication in the G1 phase. Our results showed that TgiRD1 also plays a role in controlling chromosome and centrosome reduplication. Global phosphoproteome analyses identified TgCrk4 substrates, including TgORC4, TgCdc20, TgGCP2, and TgPP2ACA. Importantly, the phylogenetic and structural studies suggest the Crk4-Cyc4 complex is limited to a minor group of the binary dividing apicomplexans.
引用
收藏
页码:2094 / 2126
页数:33
相关论文
共 50 条
  • [1] Control of the G2/M transition
    Stark, GR
    Taylor, WR
    MOLECULAR BIOTECHNOLOGY, 2006, 32 (03) : 227 - 248
  • [2] Control of the G2/M transition
    George R. Stark
    William R. Taylor
    Molecular Biotechnology, 2006, 32 : 227 - 248
  • [3] LATS1 tumor suppressor regulates G2/M transition and apoptosis
    Hong Xia
    Huilin Qi
    Yunfang Li
    Jing Pei
    James Barton
    Mark Blackstad
    Tian Xu
    Wufan Tao
    Oncogene, 2002, 21 : 1233 - 1241
  • [4] LATS1 tumor suppressor regulates G2/M transition and apoptosis
    Xia, H
    Qi, HL
    Li, YF
    Pei, J
    Barton, J
    Blackstad, M
    Xu, T
    Tao, WF
    ONCOGENE, 2002, 21 (08) : 1233 - 1241
  • [5] Checking out the G2/M transition
    Smits, VAJ
    Medema, RH
    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2001, 1519 (1-2): : 1 - 12
  • [6] GEODESICS IN G2(4)
    BUCY, RS
    JOURNAL OF DIFFERENTIAL EQUATIONS, 1994, 112 (01) : 216 - 225
  • [7] Toxoplasma gondii AP2IX-4 Regulates Gene Expression during Bradyzoite Development
    Huang, Sherri
    Holmes, Michael J.
    Radke, Joshua B.
    Hong, Dong-Pyo
    Liu, Ting-Kai
    White, Michael W.
    Sullivan, William J., Jr.
    MSPHERE, 2017, 2 (02):
  • [8] FBXO34 Regulates the G2/M Transition and Anaphase Entry in Meiotic Oocytes
    Zhao, Bing-Wang
    Sun, Si-Min
    Xu, Ke
    Li, Yuan-Yuan
    Lei, Wen-Long
    Li, Li
    Liu, Sai-Li
    Ouyang, Ying-Chun
    Sun, Qing-Yuan
    Wang, Zhen-Bo
    FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9
  • [9] 14-3-3 regulates the G2/M transition in the basidiomycete Ustilago maydis
    Mielnichuk, Natalia
    Perez-Martin, Jose
    FUNGAL GENETICS AND BIOLOGY, 2008, 45 (08) : 1206 - 1215
  • [10] Unexpected role of CDK4 in a G2/M checkpoint
    Sheppard, Karen E.
    Pearson, Richard B.
    Hannan, Ross D.
    CELL CYCLE, 2015, 14 (09) : 1351 - 1352