AUTHOR=Wang Xia , Shen Jiawei , Jiang Feng , Jin Qi 

TITLE=The Photorhabdus Virulence Cassettes RRSP-Like Effector Interacts With Cyclin-Dependent Kinase 1 and Causes Mitotic Defects in Mammalian Cells

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00366

DOI=10.3389/fmicb.2020.00366

ISSN=1664-302X

ABSTRACT=<p>The “<italic>Photorhabdus</italic> virulence cassettes” (PVCs) secreted by <italic>Photorhabdus</italic> are defined as “extracellular contractile injection systems” (eCISs) and can deliver effectors to eukaryotic hosts for cytotoxicity. Previously, we demonstrated the cryogenic electron microscopy (cryo-EM) structure and assembly process of an intact PVC particle from <italic>Photorhabdus asymbiotica</italic>. In this work, we characterized the biological functions of a PVC effector, which is defined as a homologous protein of Ras/Rap1-specific endopeptidase domain (RRSP) in the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin from <italic>Vibrio vulnificus</italic>. In this work, we found that the RRSP homologous protein (RRSP<sub>Pa</sub>) was associated with inhibition of cell proliferation and increased cell apoptosis and death of HeLa cells. Furthermore, we discovered that RRSP<sub>Pa</sub> disturbed mitotic progression, including the induction of cell cycle alteration, retardation of cell abscission time, and regression of the cleavage furrow. In addition, we revealed that RRSP<sub>Pa</sub> could target the cyclin-dependent kinase 1 (CDK1) protein and block activation of CDK1 through inhibition of Thr161 phosphorylation, which partially explained the crucial role of this effector in cell mitosis.</p>