Document Detail


Regulation of G1 phase progression by growth factors and the extracellular matrix.
MedLine Citation:
PMID:  11229819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell cycle progression is regulated by both intracellular and extracellular control mechanisms. Intracellular controls ensure that cell cycle progression is stopped in response to irregularities such as DNA damage or faulty spindle assembly, whereas extracellular factors may determine cell fate such as differentiation, proliferation or programmed cell death (apoptosis). When extracellular factors bind to receptors at the outside of the cell, signal transduction cascades are activated inside the cell that eventually lead to cellular responses. We have shown previously that MAP kinase (MAPK), one of the proteins involved in several signal transduction processes, is phosphorylated early after mitosis and translocates to the nucleus around the restriction point. The activation of MAPK is independent of cell attachment, but does require the presence of growth factors. Moreover, it appears that in Chinese hamster ovary cells, a transformed cell line, growth factors must be present early in the G1 phase for a nuclear translocation of MAPK and subsequent DNA replication to occur. When growth factors are withdrawn from the medium immediately after mitosis, MAPK is not phosphorylated, cell cycle progression is stopped and cells appear to enter a quiescent state, which may lead to apoptosis. Furthermore, in addition to this growth-factor-regulated decision point in early G1 phase, another growth-factor-sensitive period can be distinguished at the end of the G1 phase. This period is suggested to correlate with the classical restriction point (R) and may be related to cell differentiation.
Authors:
E Hulleman; J Boonstra
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  58     ISSN:  1420-682X     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-03-02     Completed Date:  2001-03-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  80-93     Citation Subset:  IM    
Affiliation:
Department of Molecular Cell Biology, University Utrecht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects
Cyclin-Dependent Kinases / antagonists & inhibitors,  metabolism
Cyclins / metabolism
Enzyme Activation / drug effects
Extracellular Matrix / metabolism*
G1 Phase / drug effects*
Growth Substances / pharmacology*
Integrins / metabolism
Mitogen-Activated Protein Kinases / metabolism
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/Cyclins; 0/Growth Substances; 0/Integrins; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinases

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