Linked Life Data

17339323

Source:http://linkedlifedata.com/resource/pubmed/id/17339323

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2007-5-7
pubmed:abstractText
Cytokinins are a class of plant hormones that regulate the cell cycle and diverse developmental and physiological processes. Several compounds have been identified that antagonize the effects of cytokinins. Based on structural similarities and competitive inhibition, it has been assumed that these anticytokinins act through a common cellular target, namely the cytokinin receptor. Here, we examined directly the possibility that various representative classical anticytokinins inhibit the Arabidopsis cytokinin receptors CRE1/AHK4 (cytokinin response 1/Arabidopsis histidine kinase 4) and AHK3 (Arabidopsis histidine kinase 3). We show that pyrrolo[2,3-d]pyrimidine and pyrazolo[4,3-d]pyrimidine anticytokinins do not act as competitors of cytokinins at the receptor level. Flow cytometry and microscopic analyses revealed that anticytokinins inhibit the cell cycle and cause disorganization of the microtubular cytoskeleton and apoptosis. This is consistent with the hypothesis that they inhibit regulatory cyclin-dependent kinase (CDK) enzymes. Biochemical studies demonstrated inhibition by selected anti-cytokinins of both Arabidopsis and human CDKs. X-ray determination of the crystal structure of a human CDK2-anticytokinin complex demonstrated that the antagonist occupies the ATP-binding site of CDK2. Finally, treatment of human cancer cell lines with anticytokinins demonstrated their ability to kill human cells with similar effectiveness as known CDK inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14356-63
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17339323-Apoptosis, pubmed-meshheading:17339323-Arabidopsis, pubmed-meshheading:17339323-Arabidopsis Proteins, pubmed-meshheading:17339323-Bone Neoplasms, pubmed-meshheading:17339323-Breast Neoplasms, pubmed-meshheading:17339323-Carrier Proteins, pubmed-meshheading:17339323-Cell Cycle, pubmed-meshheading:17339323-Cell Proliferation, pubmed-meshheading:17339323-Crystallography, X-Ray, pubmed-meshheading:17339323-Cyclin-Dependent Kinase 2, pubmed-meshheading:17339323-Cytokinins, pubmed-meshheading:17339323-Cytoskeleton, pubmed-meshheading:17339323-Flow Cytometry, pubmed-meshheading:17339323-Gene Expression Regulation, Plant, pubmed-meshheading:17339323-Humans, pubmed-meshheading:17339323-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:17339323-Osteosarcoma, pubmed-meshheading:17339323-Protein Kinases, pubmed-meshheading:17339323-Pyrimidines, pubmed-meshheading:17339323-Receptors, Cell Surface, pubmed-meshheading:17339323-Tumor Cells, Cultured
pubmed:year
2007
pubmed:articleTitle
Classical anticytokinins do not interact with cytokinin receptors but inhibit cyclin-dependent kinases.
pubmed:affiliation
Laboratory of Growth Regulators, Institute of Experimental Botany, AS CR and Palacký University, Slechtitel? 11, Olomouc, Czech Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't