Cell cycle-independent induction of D1 and D2 cyclin expression, but not cyclin-Cdk complex formation or Rb phosphorylation, by IFNgamma in macrophages.
During G1 to S phase transition, D-type cyclins form complexes with cyclin-dependent kinases (Cdk), which in turn phosphorylate retinoblastoma gene product (Rb) and inhibit its growth-inhibitory function, leading ultimately to cell proliferation. We report here a novel finding that D1 and D2 cyclins are induced in macrophages by antiproliferative factor gamma interferon (IFNgamma). The induction appears to be transcriptional activation of the D cyclin genes, since indirect events such as IFNgamma-induced colony-stimulating factor-1 (CSF-1) autocrine stimulation, alteration of D1 and D2 mRNA stability and lipopolysaccharide contamination in commercial IFNgamma preparations play no roles. In contrast to CSF-1, IFNgamma neither induces D1-Cdk4 complex formation and Rb hyperphosphorylation nor interferes with CSF-1-stimulated D1-Cdk4 interaction and Rb phosphorylation, while it completely blocks CSF-1-stimulated cell proliferation. This study suggests that induction of D1 and D2 cyclins is not necessarily associated with cell cycle progression, and D cyclins may have cell cycle-independent functions in response to IFNgamma.
Dey
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A
The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL, USA.
Li
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D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D056742:Cyclin D2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
C080336:CCND2 protein, human; C486196:Ccnd2 protein, mouse; C486197:Ccnd2 protein, rat; D056742:Cyclin D2; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; C495900:CDK4 protein, human; C495902:Cdk4 protein, mouse; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases