The Overexpression And Relationship Between Plk1 And P53 In The Colorectal Cancers

Cancer is widely considered to be a genetic disease resulting from an accumulationof various genetic abnormalities, and the most important feature of which is the cancercell could grow and proliferate larger without control, as named for immortality. Thecentrosome is believed to play a crucial role in mitosis, and related to it the Plk1(polo-likekinase 1) looks like to attract peoples'attention. A member of newly emerging family of cell-cycle regulators whose name isPOLO-like kinases have now been shown to be essential for progression through M phasein species as diverse as Drosophila, yeasts and mammals. In the eukaryotes, proteinphosphorylation plays a key role in promoting cell-cycle progression. Most prominentamong the enzymes regulating cell-cycle transitions are the cyclin-dependent kinases(CDKs),but there is no doubt that POLO kinases structurally distinct from CDKs alsomake important contributions. These kinases might either regulate the activities of CDKsor cooperate with CDKs to bring about particular cell-cycle transitions. The founding member of the PLK family, the serine/threonine proteinkinase'POLO'from Drosophila melanogaster, was identified in the course of studies onmutants displaying late larval or early pupal lethality. Mutants in the polo gene resulted ina high frequency of abnormal mitoses and aberrant chromosome segregation in larvalneuroblasts. Cell frequently displayed hypercondensed chromosomes, monopolar spindlesand disorganized spindle poles. Similar phenotypes were seen also during male meiosis,suggesting that the POLO kinase is required for spindle function in both mitosis andmeiosis. Consistent with a mitotic role, POLO kinase activity was reported to peak duringlate anaphase-telophase in syncytial embryos.Kinases related to Drosophila POLO have subsequently been characterized in organismsranging from yeast to man. Putative functional homologues of POLO have beenidentified in budding yeast,fission yeast, mammals and frogs. Based on geneticanalyses, both the Cdc5p kinase of Saccharomyces cerevisiae and the plo1 kinase ofSchizosaccharomyces pombe have been implicated in the control of mitotic and meioticevents. However,the phenotypes observed in the two organisms appear not to be strictly　　 ·96·吉林大学博士学位论文　 concordant,and no complementation between the two genes has yet been reported.Specifically, budding yeast cdc5 mutants arrest late in mitosis with partially segregatedchromosomes on an elongated spindle,suggesting that Cdc5p may mediate eventssubsequent to bipolar spindle formation. By contrast, the fission yeast plo1 kinase seemsto regulate both spindle formation and septation, as loss of plo1 function leads to either amitotic arrest, with cells exhibiting condensed chromosomes on a monopolar spindle, orto a failure in septation following nuclear division. An important regulatory function forplo1 in septation is supported by the observation that both actin ring formation and thedeposition of septal material are affected in the absence ofplo1; additionally,overexpression of plo1 can trigger septation from any point in the cell cycle. It is possiblethat PLKs may perform somewhat different functions in different organisms. Alternatively,the terminal phenotypes resulting from abrogation of PLK function may be dependent onthe precise timing of cell-cycle events in each organism. In mammals, several distinct PLKs have been identified, and it is attractive to thinkthat specific PLKs may function at different stages of the cell cycle. Among these, Plk1 ismost closely related to Drosophila POLO. As all presently known PLKs have theircatalytic domains at the N-terminus, and they share a substantial degree of sequencesimilarity, not only over their catalytic domains but also over their C-terminal domains. Inparticular, a motif of ～30 amino acids is highly conserved and may repr...