Cytokinesis is the last step of the M （mitosis） phase, yet it is crucial for the faithful division of one cell into two. Cytokinesis failure is often associated with cancer. Cytoldnesis can be morphologically divided into four steps： cleavage furrow initiation, cleavage furrow ingression, midbody formation and abscission. Molecular studies have revealed that RhoA as well as its regulators and effectors are im- portant players to ensure a successful cytokinesis. At the same time, Polo-like kinase 1 （Plkl） is an important kinase that can target many substrates and carry out different functions during mitosis, including cytokinesis. Recent studies are beginning to unveil a closer tie be- tween Plkl and RhoA networks. More specifically, Plkl phosphorylates the centralspindlin complex Cyk4 and MKLPI/CHO1, thus re- cruiting RhoA guanine nucleotide-exchange factor （GEF） Ect2 through its phosphopeptide-binding BRCT domains. Ect2 itself can be phosphorylated by Plkl in vitro. Plkl can also phosphorylate another GEF MyoGEF to regulate RhoA activity. Once activated, RhoA-GTP will activate downstream effectors, including ROCK1 and ROCK2. ROCK2 is among the proteins that associate with Plkl Polo-binding domain （PBD） in a large proteomic screen, and Plkl can phosphorylate ROCK2 in vitro. We review current understandings of the interplay between Plkl, RhoA proteins and other proteins （e.g., NudC, MKLP2, PRC 1, CEP55） involved in cytokinesis, with particular emphasis of its clinical implications in cancer.
DNA damage response (DDR) is among the most important of the mechanisms that maintain genome stability which, when destabilized, predisposes organs to cancer. Reversible phosphorylation mediated by protein kinases and protein phosphatases regulates most, if not all, cellular activities, including DDR. Protein kinase inhibitors have become the main focus of targeted therapy and anticancer drug development. However, our limited knowledge of protein phosphatase function is compromising our capacity to develop therapeutic agents against phosphatases. In this review, we summarize the roles of serine/threonine protein phosphatases involved in DDR and propose that in situ dephosphorylation of phosphoproteins by protein phosphatases, instead of proteasome-mediated degradation of phosphoproteins, is mainly employed by cells.
