Document Detail

Single amino acid (arginine) deprivation induces G1 arrest associated with inhibition of cdk4 expression in cultured human diploid fibroblasts.
MedLine Citation:
PMID:  10694439     Owner:  NLM     Status:  MEDLINE    
Withdrawal of a single amino acid (arginine) from freely cycling early passage primary human fibroblasts caused a halt to proliferation, characterized by an accumulation of cells in the G1 phase of the cell cycle. This arrest was accompanied by the suppression of cyclin D1- and cyclin E-associated kinase activities and the appearance of hypophosphorylated retinoblastoma protein. Arginine-deprived cells remained viable for in excess of 4 days and could be made to synchronously reenter the cell cycle by restoration of the amino acid, with kinetics characteristic of exit from a quiescent state. Stimulation of cells arrested by serum withdrawal did not result in S-phase entry when arginine was omitted from the culture medium. Although cyclin D1 accumulated on normal schedule, cdk4, which increased following restimulation in amino acid-replete medium, was not induced when arginine was absent. These results suggest that arginine deprivation-in common with other "suboptimal" conditions-inhibits the passage of normal human cells through the restriction point and implicate cdk4 as the key regulatory element in amino acid-sensitive cell cycle control.
J Lamb; D N Wheatley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental cell research     Volume:  255     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-24     Completed Date:  2000-04-24     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  238-49     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Cell Pathology, University of Aberdeen, MacRobert Building, 581 King Street, Aberdeen, AB24 5UA, Scotland, United Kingdom.
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MeSH Terms
Amino Acid Substitution
Cells, Cultured
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases / biosynthesis*,  genetics
Fibroblasts / metabolism*,  pathology*
G1 Phase*
Gene Expression Regulation
Proto-Oncogene Proteins*
Structure-Activity Relationship
Reg. No./Substance:
0/Proto-Oncogene Proteins; 74-79-3/Arginine; EC protein, human; EC Kinase 4; EC Kinases

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