Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
2003-10-6
pubmed:abstractText
The protein kinase C (PKC) family consists of multiple isoforms that are involved in the regulation of diverse cellular responses. Suppression of PKC induces growth arrest in various types of cells. However, the underlying molecular mechanisms have not been thoroughly investigated. In this report, we demonstrated that the concurrent inhibition, rather than separate inhibition, of phorbol ester-dependent PKC alpha and theta isoforms is crucial for the induction of G1 cell cycle arrest and that this negative cell cycle regulation is via p53-independent mechanisms. PKC suppression-mediated growth arrest is associated with the induction of cell cycle inhibitor p21WAF1/CIP1 and the occurrence of hypophosphorylated Rb. The G1 checkpoint induced by the suppression of PKC occurs not only in murine Swiss3T3 but also in p53-deficient cells and human lung cancer cells containing mutated p53. Luciferase and nuclear run-off assays demonstrated that p21WAF1/CIP1 is, in part, transcriptionally regulated in response to the suppression of PKC alpha and theta. However, the stability of p21 mRNA is also augmented after the addition of PKC alpha and theta antisense oligonucleotides, indicating the involvement of post-transcriptional mechanisms in p21WAF1/CIP1 expression. These data suggest the existence of a cell cycle checkpoint pathway regulated by PKC alpha and theta isoforms. Furthermore, our findings support the notion that G1 checkpoint control can be restored in tumor cells containing abnormal p53, by targeting the PKC-regulated p21WAF1/CIP1 induction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CDK4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Cyclins, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides, Antisense, http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PRKCQ protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Prkca protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Prkcq protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39782-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12896972-3T3 Cells, pubmed-meshheading:12896972-Animals, pubmed-meshheading:12896972-Base Sequence, pubmed-meshheading:12896972-Cyclin D, pubmed-meshheading:12896972-Cyclin-Dependent Kinase 4, pubmed-meshheading:12896972-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:12896972-Cyclin-Dependent Kinases, pubmed-meshheading:12896972-Cyclins, pubmed-meshheading:12896972-Enzyme Inhibitors, pubmed-meshheading:12896972-G1 Phase, pubmed-meshheading:12896972-Gene Deletion, pubmed-meshheading:12896972-Genes, p53, pubmed-meshheading:12896972-Humans, pubmed-meshheading:12896972-Isoenzymes, pubmed-meshheading:12896972-Mice, pubmed-meshheading:12896972-Oligodeoxyribonucleotides, Antisense, pubmed-meshheading:12896972-Protein Kinase C, pubmed-meshheading:12896972-Protein Kinase C-alpha, pubmed-meshheading:12896972-Proto-Oncogene Proteins, pubmed-meshheading:12896972-Retinoblastoma Protein, pubmed-meshheading:12896972-Transcription, Genetic, pubmed-meshheading:12896972-Tumor Suppressor Protein p53
pubmed:year
2003
pubmed:articleTitle
A p53-independent G1 cell cycle checkpoint induced by the suppression of protein kinase C alpha and theta isoforms.
pubmed:affiliation
Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't