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PMID: 7559779 Published · ppublish English Journal Article

Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells.

The Journal of cell biology ·Vol. 131 ·No. 1 ·1995-10-00 ·Pages 227-34

Kranenburg O, Scharnhorst V, Van der Eb AJ, Zantema A

Abstract

Studies on the molecular mechanisms underlying neuronal differentiation are frequently performed using cell lines established from neuroblastomas. In this study we have used mouse N1E-115 neuroblastoma cells that undergo neuronal differentiation in response to DMSO. During differentiation, cyclin-dependent kinase (cdk) activities decline and phosphorylation of the retinoblastoma gene product (pRb) is lost, leading to the appearance of a pRb-containing E2F DNA-binding complex. The loss of cdk2 activity is due to a decrease in cdk2 abundance whereas loss of cdk4 activity is caused by strong association with the cdk inhibitor (CKI) p27KIP1 and concurrent loss of cdk4 phosphorylation. Moreover, neuronal differentiation can be induced by overexpression of p27KIP1 or pRb, suggesting that inhibition of cdk activity leading to loss of pRb phosphorylation, is the major determinant for neuronal differentiation.

MeSH Terms
Animals Base Sequence CDC2-CDC28 Kinases Carrier Proteins Cell Cycle Proteins Cell Differentiation/physiology Cell Division/physiology Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases/antagonists & inhibitors,metabolism DNA-Binding Proteins E2F Transcription Factors Enzyme Inhibitors/metabolism Mice Microtubule-Associated Proteins/metabolism Molecular Sequence Data Neuroblastoma/enzymology,pathology Phosphorylation Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism Proto-Oncogene Proteins Retinoblastoma Protein/metabolism Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors/metabolism Tumor Cells, Cultured/enzymology Tumor Suppressor Proteins
Chemicals
Arid4a protein, mouse Carrier Proteins Cdkn1b protein, mouse Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors Enzyme Inhibitors Microtubule-Associated Proteins Proto-Oncogene Proteins Retinoblastoma Protein Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Protein Serine-Threonine Kinases CDC2-CDC28 Kinases Cdk2 protein, mouse Cdk4 protein, mouse Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kranenburg O
Sylvius Laboratory, Department of Molecular Carcinogenesis, Leiden University, The Netherlands.
Scharnhorst V
Van der Eb A J
Zantema A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.131.1.227
Published
1995-10-00
Pages
227-34
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120591
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.131.1.227 PMC Full Text View journal details
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