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rdf:type |
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lifeskim:mentions |
umls-concept:C0007586,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0205421,
umls-concept:C0243045,
umls-concept:C0288331,
umls-concept:C0376515,
umls-concept:C0598086,
umls-concept:C0598388,
umls-concept:C0702240,
umls-concept:C1332397,
umls-concept:C1415887,
umls-concept:C1419040,
umls-concept:C1420433,
umls-concept:C1424666,
umls-concept:C1550548,
umls-concept:C1555714,
umls-concept:C1705654
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pubmed:issue |
51
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pubmed:dateCreated |
2002-11-6
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pubmed:abstractText |
The anti-apoptotic molecules BCL-x(L) and BCL2 delay cell cycle entry from quiescence. We used serum induction and induction of a Myc-estrogen receptor fusion protein (MycER) in quiescent fibroblasts to investigate the mechanisms underlying the cell cycle activity of BCL-x(L) and BCL2. We demonstrate for the first time that BCL-xL and BCL2 delayed serum-induced and Myc-induced, but not E2F-induced, cell cycle entry. The cyclin-dependent kinase inhibitor p27 was elevated during serum deprivation and cell cycle entry in BCL-x(L) or BCL2-expressing NIH3T3 cells and a Rat1MycER cell line. Activation of cyclin-dependent kinase 2 (cdk2) and cyclin-dependent kinase 4 (cdk4) were delayed during progression to S phase, while the induction of cyclin D1 protein, as well as the levels of cyclin E, cdk2, and cdk4 were unaltered by BCL-x(L) or BCL2. Inhibition of cyclin/cdk activities in BCL-x(L) or BCL2 expressing cells was associated with excess p27 in the cyclin/cdk complexes. Neither BCL-x(L) nor BCL2 delayed S phase entry in cells deficient in p27, thus p27 is required for the cell cycle function of BCL-x(L) and BCL2. The cell cycle effects of BCL-x(L) and BCL2 were more profound in Myc-induced than in serum-induced cell cycle entry. Our results suggest that one possible mechanism by which BCL-x(L) and BCL2 delay cell cycle entry may be the inhibition of Myc activity through the elevation of p27.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/CCND2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CCND3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDK4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D3,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin E,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2F Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tetracycline,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7765-75
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12420213-Humans,
pubmed-meshheading:12420213-Animals,
pubmed-meshheading:12420213-Mice,
pubmed-meshheading:12420213-Cattle,
pubmed-meshheading:12420213-Rats,
pubmed-meshheading:12420213-Culture Media,
pubmed-meshheading:12420213-Tetracycline,
pubmed-meshheading:12420213-Fetal Blood,
pubmed-meshheading:12420213-Cell Cycle,
pubmed-meshheading:12420213-S Phase,
pubmed-meshheading:12420213-G1 Phase,
pubmed-meshheading:12420213-3T3 Cells,
pubmed-meshheading:12420213-Culture Media, Serum-Free,
pubmed-meshheading:12420213-Gene Expression Regulation,
pubmed-meshheading:12420213-DNA-Binding Proteins,
pubmed-meshheading:12420213-Receptors, Estrogen
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