title: Role of polyamines at the G1/S boundary and G2/M phase of the cell cycle.
abstract: The role of polyamines at the G1/S boundary and in the G2/M phase of the cell cycle was studied using synchronized HeLa cells treated with thymidine or with thymidine and aphidicolin. Synchronized cells were cultured in the absence or presence of α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, plus ethylglyoxal bis(guanylhydrazone) (EGBG), an inhibitor of S-adenosylmethionine decarboxylase. When polyamine content was reduced by treatment with DFMO and EGBG, the transition from G1 to S phase was delayed. In parallel, the level of p27(Kip1) was greatly increased, so its mechanism was studied in detail. Synthesis of p27(Kip1) was stimulated at the level of translation by a decrease in polyamine levels, because of the existence of long 5'-untranslated region (5'-UTR) in p27(Kip1) mRNA. Similarly, the transition from the G2/M to the G1 phase was delayed by a reduction in polyamine levels. In parallel, the number of multinucleate cells increased by 3-fold. This was parallel with the inhibition of cytokinesis due to an unusual distribution of actin and α-tubulin at the M phase. Since an association of polyamines with chromosomes was not observed by immunofluorescence microscopy at the M phase, polyamines may have only a minor role in structural changes of chromosomes at the M phase. In general, the involvement of polyamines at the G2/M phase was smaller than that at the G1/S boundary.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Saiki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okudaira
authors.forename: Mayuko
authors.initials: M
authors.lastname: Tome
authors.forename: Kyohei
authors.initials: K
authors.lastname: Higashi
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Terui
authors.forename: Kunio
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015317:Biogenic Polyamines / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology*; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008935:Mitoguazone / Q000031:analogs & derivatives / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D016196:S Phase / Q000187:drug effects / Q000502:physiology*
chemical_list: D015317:Biogenic Polyamines; C436291:CDKN1B protein, human; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D050760:Cyclin-Dependent Kinase Inhibitor p27; C041127:ethylglyoxal bis(guanylhydrazone); D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone; D000518:Eflornithine