Geldanamycin induces cell cycle arrest in K562 erythroleukemic cells.
Geldanamycin (GA), a benzoquinone ansamycin, is one of the specific inhibitors of 90-kDa heat shock protein and induces growth inhibition and apoptosis in certain cancer cell lines. We have investigated the mechanism of GA-induced growth inhibition in K562 erythroleukemic cells. DNA flow-cytometric analysis indicated that GA-induced growth arrest was associated with G2/M phase arrest of the cell cycle. GA treatment down-regulated the expression of cyclin B1 and inhibited phosphorylation of Cdc2 protein, both key regulatory proteins at the G2/M boundary. GA also markedly inhibited the Cdc2 kinase activity, which may be in part a result of up-regulation of p27KIP1 by GA. The present results suggest a novel mechanism that p27KIP1 could be involved in the regulation of G2 to M phase transition.
Kim
H R
HR
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Korea.
Lee
C H
CH
Choi
Y H
YH
Kang
H S
HS
Kim
H D
HD
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016227:Benzoquinones; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016195:G2 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells / Q000473:pathology*; D047029:Lactams, Macrocyclic; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008938:Mitosis / Q000187:drug effects; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D006131:Growth Inhibitors; D047029:Lactams, Macrocyclic; D008869:Microtubule-Associated Proteins; D011809:Quinones; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016203:CDC2 Protein Kinase; C001277:geldanamycin