p27(Kip1) enhances myelin basic protein gene promoter activity.
The process of oligodendrocyte differentiation is a complex event that requires cell cycle withdrawal, followed by the activation of a specific transcriptional program responsible for the synthesis of myelin genes. Because growth arrest precedes differentiation, we sought to investigate the role of cell cycle molecules in the activation of myelin gene promoters. We hypothesized that the cell cycle inhibitor p27(Kip1), which is primarily responsible for arresting proliferating oligodendrocyte progenitors, may be involved in the transcriptional regulation of myelin genes. In agreement with this hypothesis, overexpression of p27(Kip1) in the CG4 cell line, but not in 3T3 fibroblasts, enhances the expression of luciferase driven by the myelin basic protein (MBP) promoter. Interestingly, this effect is specific for p27(Kip1); overexpression of other cell cycle inhibitors had no effect. Additionally, this effect is independent of halting the cell cycle; treatment with the cell cycle blocker roscovitine did not affect MBP promoter usage. We conclude that p27(Kip1) contributes to oligodendrocyte differentiation by regulating transcription of the MBP gene.
Miskimins
Robin
R
Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, SD 57069, USA. rmiskim@usd.edu
Srinivasan
Rekha
R
Marin-Husstege
Mireya
M
Miskimins
W Keith
WK
Casaccia-Bonnefil
Patrizia
P
D016475:3T3 Cells; D000818:Animals; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D017930:Genes, Reporter / Q000502:physiology; D008156:Luciferases / Q000235:genetics; D051379:Mice; D004676:Myelin Basic Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493961:Cdkn1b protein, mouse; C493965:Cdkn1c protein, mouse; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D004676:Myelin Basic Protein; D009687:Nuclear Proteins; D011687:Purines; D025521:Tumor Suppressor Proteins; D000077546:Roscovitine; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases