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Altered composition and DNA binding activity of the AP-1 transcription factor during the ageing of human fibroblasts. 2001

A Sheerin, and K S Thompson, and M H Goyns
School of Health Sciences, Molecular Gerontology Unit, University of Sunderland, Fleming Building, Wharncliffe Street, Sunderland SR1 3SD, UK.

We have investigated the expression of AP-1 transcription factor proteins during the in-vitro ageing of human fibroblasts. The numbers of these cells that are in the cell cycle gradually decreases up to 45 cumulative population doublings (cPD), thereafter the decline is steeper, until almost all cells enter a post-mitotic state by 60 cPD. We observed that a 34 kd junB species began to replace the 44 kd junB species after 41 cPD. This was followed, after 44 cPD, by a loss of fra1 and both junD species. After 49 cPD there was a gradual decline in the levels of fos and jun proteins, but disproportionately, so that the fos/jun protein ratio also declined. Although fos and jun proteins were still clearly present at 60 cPD, utilisation of the AP-1 DNA consensus sequence could not be demonstrated after 54 cPD. These data indicate that significant changes occur in the composition of the AP-1 transcription factor during ageing, but also that alterations in its DNA binding activity may involve other factors.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D016755 Proto-Oncogene Proteins c-jun Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun. c-fos-Associated Protein p39,c-jun Proteins,fos-Associated Protein p39,jun B Proteins,jun D Proteins,jun Proto-Oncogene Proteins,p39(c-jun),Proto-Oncogene Products c-jun,Proto-Oncogene Proteins jun,jun Proto-Oncogene Product p39,p39 c-jun,Proto Oncogene Products c jun,Proto Oncogene Proteins c jun,Proto Oncogene Proteins jun,c fos Associated Protein p39,c jun Proteins,fos Associated Protein p39,jun Proto Oncogene Product p39,jun Proto Oncogene Proteins,p39 c jun
D016760 Proto-Oncogene Proteins c-fos Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes. Fos B Protein,Fos-Related Antigen,Fos-Related Antigens,c-fos Protein,c-fos Proteins,fos Proto-Oncogene Protein,fos Proto-Oncogene Proteins,p55(c-fos),Antigens, Fos-Related,FRAs,Proto-Oncogene Products c-fos,Proto-Oncogene Proteins fos,p55 c-fos,Antigen, Fos-Related,Fos Related Antigen,Fos Related Antigens,Protein, c-fos,Protein, fos Proto-Oncogene,Proto Oncogene Products c fos,Proto Oncogene Proteins c fos,Proto Oncogene Proteins fos,Proto-Oncogene Protein, fos,c fos Protein,c fos Proteins,fos Proto Oncogene Protein,fos Proto Oncogene Proteins,p55 c fos
D016922 Cellular Senescence Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS. Aging, Cell,Cell Aging,Cell Senescence,Replicative Senescence,Senescence, Cellular,Senescence, Replicative,Cell Ageing,Cellular Ageing,Cellular Aging,Ageing, Cell,Ageing, Cellular,Aging, Cellular,Senescence, Cell
D051921 Fos-Related Antigen-2 A basic-leucine zipper transcription factor that is closely related to C-FOS PROTEINS. It forms heterodimeric complexes with C-JUN PROTEINS to regulate GENE transcription. Fra-2 Transcription Factor,Fos Related Antigen 2,Transcription Factor, Fra-2

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