The polo-like kinase Plx1 prevents premature inactivation of the APCFizzy-dependent pathway in the early Xenopus cell cycle

Xenopus Polo-like kinase Plx1: a multifunctional mitotic kinase

“…Plx1 is suggested to antagonize an unidentified microcystin-sensitive phosphatase that inactivates the APC/C. Evidence in Xenopus egg extracts indicates that microcystin suppresses the requirement for Plx1 in Ca 2 þ -dependent exit from meiosis, and also prevents APC/C inactivation in the early mitotic cell cycle (Brassac et al, 2000). Despite the progress in this area, much work needs to be carried out to thoroughly understand the exact mechanism of Plx1's involvement in mitotic exit.…”

“…Plx1 activity is clearly required to activate this pathway, as demonstrated by the inhibition of cyclin B degradation by dominant negative Plx1 (Descombes and Nigg, 1998;Qian et al, 1999;Liu et al, 2004). The current models of APC/C activity regulation by Plx1 include direct phosphorylation of APC/C subunits and activation of the APC/C (Kotani et al, 1998;Rudner and Murray, 2000;Golan et al, 2002), regulation of the association of APC/C regulators with the ubiquitin ligase (Moshe et al, 2004), and preventing the APC/C from premature inactivation (Brassac et al, 2000). Some of these models either lack in vivo evidence or require confirmation in other laboratories.…”

“…The third mechanism, proposed by Brassac et al (2000), suggests that besides activating the APC/C, Plx1 is also required to prevent premature inactivation of the APC/C. They reasoned that because Fizzy-related/cdh1 is not expressed during early embryonic mitotic cell cycles, at least in Drosophila and Xenopus (Sigrist and Lehner, 1997;Lorca et al, 1998), Fizzy/Cdc20-dependent APC/C activity must be sustained long enough to maintain low Cdc2/cyclin B activity after completion of mitosis to allow reassembly of functional nuclei and DNA synthesis.…”

The anaphase-promoting complex: a key factor in the regulation of cell cycle

“…Degradation of Cdc5 in budding yeast is mediated by APC Cdh1 and expression of a nondegradable Cdc5 arrests cells in a G2-like state, lacking mitotic cyclins and a mitotic spindle, suggesting that destruction of this protein is required to inactivate APC-dependent degradation of mitotic cyclins as cells enter S phase (Charles et al, 1998;Shirayama et al, 1998). Accordingly, immunoprecipitation of Plx1 from interphasic Xenopus egg extracts in which APC has been activated by the addition of purified cyclin B/cdk1 induces premature inactivation of cyclin B degradation (Brassac et al, 2000).…”

Sak/Plk4 and mitotic fidelity

“…For example, in the Drosophila syncytium, only partial destruction of cyclin B at spindle poles and centromeres occurs between mitoses, but with cellularization of the embryo, destruction of cyclin B is nearly complete between cell cycles (Su et al, 1998). In early Drosophila and Xenopus embryogenesis, mitotic exit depends only on fizzy (Cdc20), while fizzy-related (Cdh1) is not expressed until the larval stage of development, when APC-Cdh1 is required for complete destruction of mitotic cyclins (Sigrist and Lehner, 1997;Brassac et al, 2000). In this regard, cell division occurs until the postgastrula stage in Sak À/À embryos, at which point cyclin B1 persists and late anaphase arrest is evident, suggesting that APC-Cdh1 activity may be insufficient.…”