Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-10-1
pubmed:abstractText
Current models suggest that cyclin B1/cdk1 regulates the G2 to M transition and that its activity is maximal during the period from prophase to metaphase in mammalian cells. Although data are lacking, the idea that cyclin B1/cdk1 regulates the transit time from prophase to metaphase is reasonable. Development of small molecule inhibitors of cyclin dependent kinases (cdk's) as cancer therapeutics presents an opportunity to evaluate the effects of inhibiting cdk's in asynchronous cell populations. Analysis of cdk1 inhibitors is complicated by their ability to inhibit other cdk's in vitro at higher concentrations. In this study we measured the effects of two cdk1 inhibitors on S, G2, and M transit for Hela cells and correlated these effects on cyclin B1/cdk1 and cyclin A/cdk2 activities. Dose responses demonstrate that low concentrations of both compounds inhibited the activity of cdk1 but not cdk2 in HeLa cells. The partial loss of cdk1 activity at low doses induced a prophase accumulation during a 3 h period and an increased transit time through mitosis. In addition, both inhibitors lengthened the G2 transit time with progressively greater effect on mid and late G2. High doses of both inhibitors increased the S phase time, which correlated with the inhibition of cdk2 activity. These results suggest that cdk1-cyclin activity is rate limiting for cell cycle progression during a period from mid G2 through prophase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1538-4101
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
349-57
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Inhibition of cdk1 by alsterpaullone and thioflavopiridol correlates with increased transit time from mid G2 through prophase.
pubmed:affiliation
Environmental Health Sciences Department, Case Western Reserve University, Cleveland, Ohio, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.