[Advance of study on effects of Chfr gene of mitosis prophase checkpoint--review].
Chfr, a mitotic stress checkpoint gene, regulates a prophase delay in cells exposed to agents that disrupt microtubules, such as nocodazole and taxol. Chfr expression was ubiquitious in normal human tissues. It is very high conserved between human and mice. Preliminary sutdies indicated that Chfr expression was cell cycle regulated and it dependent on its ubiqitin ligase activity. The direct target of the Chfr pathway was Polo-like kinase 1 (Plk1). Ubiquitination of Plk1 by Chfr delayed the activation of the Cdc25C phosphatase and the inactivation of the Weel kinase, leading to a delay in Cdc 2 activation. The chfr gene was inactivated owing to lack of expression or by mutation in some human cancer cell lines examined. Normal primary cells and tumour cell lines that express wild-type chfr exhibited delayed entry into metaphase when centrosome separation was inhibited by mitotic stress. In contrast, the tumour cell lines that had lost chfr function entered metaphase without delay. Ecotopic expression of wild-type chfr restored the cell cycle delay and increased the ability of the cells to survive mitotic stress. Thus, chfr defines a checkpoint that delays entry into metaphase in response to mitotic stress. The progress of research on structure of Chfr gene and effects of Chfr protein was reviewed.
Gong
Hui
H
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wnhan 430030, China.
D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008677:Metaphase / Q000235:genetics / Q000502:physiology; D008938:Mitosis / Q000235:genetics* / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000075223:Poly-ADP-Ribose Binding Proteins; D011418:Prophase / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D044767:Ubiquitin-Protein Ligases; D000097869:Polo-Like Kinase 1; C412002:CHFR protein, human; C066780:Clk dual-specificity kinases