Development and application of bioprobes for Mammalian cell cycle analyses.
In this review, I have mainly described the cell cycle inhibitors isolated from microbial metabolites. Once the molecular target of the inhibitor is determined, the inhibitor can be used as bioprobe to dissect the diverse aspect of biological functions in chemical biology research. Reveromycin A and phosmidosine inhibited the protein synthesis of mammalian cells and arrested the cell cycle at G1 phase. Lucilactaene arrested cells at G1 phase through restoration of mutant p53. Tryprostatin A inhibited the microtubule polymerization by interfering with the interaction between tubulin and microtubule associating protein. On the contrary, cyclotryprostatin D, structurally related to tryprostatin A, enhanced the tubulin polymerization. Terpendole E inhibited the motor activity of mitotic kinesin, Eg5 and induced monoastral spindle in M phase.
Osada
Hiroyuki
H
Antibiotics Laboratory, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan. antibiot@postman.riken.go.jp
D000818:Animals; D001419:Bacteria / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D003864:Depression, Chemical; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D005663:Furans / Q000378:metabolism / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D008322:Mammals; D008938:Mitosis / Q000187:drug effects; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology; D011685:Purine Nucleotides / Q000378:metabolism / Q000494:pharmacology; D011714:Pyrans / Q000378:metabolism / Q000494:pharmacology; D011758:Pyrroles / Q000378:metabolism / Q000494:pharmacology; D013141:Spiro Compounds / Q000378:metabolism / Q000494:pharmacology
D004224:Diterpenes; D005663:Furans; D006131:Growth Inhibitors; D026121:Indole Alkaloids; D007211:Indoles; D010879:Piperazines; D011685:Purine Nucleotides; D011714:Pyrans; D011758:Pyrroles; D013141:Spiro Compounds; C444204:lucilactaene; C477863:terpendole E; C097858:tryprostatin A; C068098:reveromycin A; C068885:phosmidosine