Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation

X M Tang; J S Beesley; J B Grinspan; P Seth; J Kamholz; F Cambi

doi:10.1002/(SICI)1097-4644(20000201)76:2<270::AID-JCB10>3.0.CO;2-6

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Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation

Journal article

Peer reviewed

Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation

X M Tang, J S Beesley, J B Grinspan, P Seth, J Kamholz and F Cambi

Journal of cellular biochemistry, Vol.76(2), pp.270-279

12/1999

DOI: 10.1002/(SICI)1097-4644(20000201)76:2<270::AID-JCB10>3.0.CO;2-6

PMID: 10618643

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Abstract

Oligodendrocyte differentiation is accompanied by dramatic changes in gene expression as well as cell cycle arrest. To determine whether cell cycle arrest is sufficient to induce the changes in cell phenotype associated with differentiation, we inhibited oligodendrocyte precursor proliferation in vitro by overexpressing p27, a cyclin kinase inhibitor, using a recombinant adenovirus. Ectopic expression of p27 efficiently inhibited oligodendrocyte precursor cell division, even in the presence of exogenous mitogens, by blocking the activity of the cyclin-dependent kinase, cdk2. Although the cells had stopped dividing, they did not express galactocerebroside (GalC) or myelin basic protein (MBP), changes associated with oligodendrocyte differentiation, suggesting that they had not differentiated. After removal of exogenous mitogens, however, adenovirus-expressing oligodendrocyte precursors differentiated with a temporal profile similar to that of control, uninfected oligodendrocytes, as indicated by expression of GalC and MBP. We conclude that cell cycle arrest is not sufficient to induce differentiation of dividing oligodendrocyte precursors, and that modulation of additional, as yet unknown, signaling pathways is required for this to occur.

Gene Expression

Oligodendroglia - metabolism

CDC2-CDC28 Kinases

Enzyme Inhibitors - metabolism

Microtubule-Associated Proteins - genetics

Microtubule-Associated Proteins - metabolism

Cells, Cultured

Rats

Stem Cells - cytology

Stem Cells - metabolism

Cyclin-Dependent Kinase 5

Cyclin-Dependent Kinase Inhibitor p27

Cyclin-Dependent Kinase 2

Animals

Protein-Serine-Threonine Kinases - antagonists & inhibitors

Adenoviridae - genetics

Cell Cycle - physiology

Cyclin-Dependent Kinases - antagonists & inhibitors

Oligodendroglia - cytology

Genetic Vectors

Cell Differentiation - physiology

Cell Cycle Proteins

Tumor Suppressor Proteins

Details

Title: Subtitle: Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation
Creators: X M Tang - Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
J S Beesley
J B Grinspan
P Seth
J Kamholz
F Cambi
Resource Type: Journal article
Publication Details: Journal of cellular biochemistry, Vol.76(2), pp.270-279
Publisher: United States
DOI: 10.1002/(SICI)1097-4644(20000201)76:2<270::AID-JCB10>3.0.CO;2-6
PMID: 10618643
ISSN: 0730-2312
eISSN: 1097-4644
Grant note: NS01726 / NINDS NIH HHS NS34017 / NINDS NIH HHS
Language: English
Date published: 12/1999
Academic Unit: Neurology; Psychiatry
Record Identifier: 9984020888202771

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