| Single amino acid (arginine) deprivation induces G1 arrest associated with inhibition of cdk4 expression in cultured human diploid fibroblasts. | |
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MedLine Citation:
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PMID: 10694439 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J Lamb; D N Wheatley |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental cell research Volume: 255 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2000 Mar |
Date Detail:
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Created Date: 2000-04-24 Completed Date: 2000-04-24 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 238-49 Citation Subset: IM |
Copyright Information:
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Copyright 2000 Academic Press. |
Affiliation:
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Department of Cell Pathology, University of Aberdeen, MacRobert Building, 581 King Street, Aberdeen, AB24 5UA, Scotland, United Kingdom. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Arginine Cells, Cultured Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases / biosynthesis*, genetics Fibroblasts / metabolism*, pathology* G1 Phase* Gene Expression Regulation Humans Proto-Oncogene Proteins* Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Proto-Oncogene Proteins; 74-79-3/Arginine; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases |
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