Down-regulation of the retinoblastoma protein (rb) is associated with rat oligodendrocyte differentiation.
Terminal differentiation of oligodendrocytes is associated with permanent withdrawal from the cell cycle. We studied the expression of the retinoblastoma protein, expression and activity of G1 cyclins and kinases in oligodendrocyte progenitor cells cultured in vitro. We found that Rb stopped to be expressed concomitantly with the activation of CNPase in oligodendrocytes differentiated with thyroid hormone. In contrast, Rb continued to be expressed at reduced levels in oligodendrocytes that were arrested in G1 by removal of mitogens. Cyclin D1, cdk2, and cdk4 kinase activities were decreased in G1-arrested and differentiated oligodendrocytes. Cyclin E, however, continued to be expressed in G1-arrested oligodendrocytes. Inhibition of differentiation induced by mitogens in oligodendrocytes arrested in G1 by Ad-p27 was accompanied by continued expression of Rb, D1, and E cyclins. After removal of mitogens and addition of thyroid hormone, Rb stopped being expressed and CNPase expression was activated with a temporal course similar to that of oligodendrocytes infected with a control adenovirus. Our results indicate that Rb may play an important function in differentiation of oligodendrocytes in response to external mitogens and differentiation factors.
Huang
Zhong
Z
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Tang
Xue-Ming
XM
Cambi
Franca
F
D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D000943:Antigens, Differentiation; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D003470:Culture Media; D016213:Cyclins; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; C488961:oligodendrocyte O antigen, rat; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; C495903:Cdk4 protein, rat; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases