Cell cycle control of Schwann cell proliferation: role of cyclin-dependent kinase-2.
Schwann cell proliferation is regulated by multiple growth factors and axonal signals. However, the molecules that control growth arrest of Schwann cells are not well defined. Here we describe regulation of the cyclin-dependent kinase-2 (CDK2) protein, an enzyme that is necessary for the transition from G1 to S phase. Levels of CDK2 protein were elevated in proliferating Schwann cells cultured in serum and forskolin. However, when cells were grown with either serum-free media or at high densities, CDK2 levels declined to low levels. The decrease in CDK2 levels was associated with growth arrest of Schwann cells. The modulation of CDK2 appears to be regulated at the transcriptional level, because CDK2 mRNA levels and its promoter activity both decline during cell cycle arrest. Furthermore, analysis of the CDK2 promoter suggests that Sp1 DNA binding sites are essential for maximal activation in Schwann cells. Together, these data suggest that CDK2 may represent a significant target of developmental signals that regulate Schwann cell proliferation and that this regulation is mediated, in part, through regulation of Sp1 transcriptional activity.
Tikoo
R
R
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
Zanazzi
G
G
Shiffman
D
D
Salzer
J
J
Chao
M V
MV
D000818:Animals; D000831:Animals, Newborn; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology*; D014158:Transcription, Genetic
D016895:Culture Media, Serum-Free; D011518:Proto-Oncogene Proteins; D005576:Colforsin; 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