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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1993-11-22
pubmed:abstractText
cis-Diamminedichloroplatinum(II) (CDDP) induced G2-phase arrest in PC-9 human cancer cells. To elucidate how CDDP acts on cell-cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as p34cdc2 protein kinase. p34cdc2 protein kinase activity was maximum in G2 phase and decreased after G2/M transition in synchronized PC-9 human lung cancer cells. Evidence for a phosphorylated p34cdc2 protein kinase complexed with cyclin B was obtained from cells in G2 phase and the p34cdc2 protein kinase appeared to be dephosphorylated at M phase. After exposure to CDDP in G1 phase, PC-9 cells were arrested in G2 phase. The activation of p34cdc2 protein kinase was inhibited by CDDP. Cyclin A and wee-I kinase were not affected by the exposure to CDDP. Cyclin B was degraded in M phase in PC-9 cells. Exposure to CDDP did not affect the degradation of cyclin B. Our data suggest that the effect of CDDP on cell-cycle phase might be regulated by the dephosphorylation of p34cdc2 protein kinase. To determine whether the p34cdc2 protein kinase is a primary target for CDDP, we examined the direct effect of CDDP on tyrosine dephosphorylation of p34cdc2 protein kinase in cellular extracts. Cell lysates from synchronized PC-9 in G2 phase were immunoprecipitated with p13-Sepharose beads. In vitro dephosphorylation of phosphotyrosine of p34cdc2 protein kinase was observed after exposure to okadaic acid in a concentration-dependent manner. The dephosphorylation of p34cdc2 protein kinase by okadaic acid was inhibited by CDDP. We hypothesize that inhibition of p34cdc2 dephorphorylation by CDDP is important for its growth-inhibiting properties.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
616-22
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Cis-diamminedichloroplatinum(II) inhibits p34cdc2 protein kinase in human lung-cancer cells.
pubmed:affiliation
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't