Transcription Factor Ap-1 Activity Is Required for Initiation of DNA Synthesis and Is Lost During Cellular Aging

Riabowol, K., Schiff, J., Gilman, M. Z. (January 1992) Transcription Factor Ap-1 Activity Is Required for Initiation of DNA Synthesis and Is Lost During Cellular Aging. Proceedings of the National Academy of Sciences of the United States of America, 89 (1). pp. 157-161. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/1729683

Abstract

Activation of the AP-1 complex of transcription factors is one of the earliest nuclear responses to mitogenic stimuli. We demonstrate directly that AP-1 activity is required for human cells to proliferate in response to serum. We also rind that activity of the AP-1 complex is selectively reduced in old human fibroblasts prior to their entering a fully senescent state. Levels of Fos protein induced through diverse signal transduction pathways, the amount of AP-1 DNA binding activity in vitro, and the activity of an AP-1-dependent reporter gene in vivo are substantially decreased as fibroblasts age. Moreover, the composition of the AP-1 complex changes, so that old cells produce predominantly Jun-Jun homodimers instead of Fos-Jun heterodimers. Changes in AP-1 activity may be due in part to changes in posttranslational modification of Fos protein that impair its ability to form active DNA-binding heterodimers with Jun. These data suggest that changes in AP-1 activity may contribute to the inability of senescent cells to proliferate in response to mitogens.

Item Type:	Paper
Uncontrolled Keywords:	FOS JUN CELLULAR SENESCENCE SIGNAL TRANSDUCTION SENESCENT HUMAN-FIBROBLASTS GROWTH-FACTORS ANTISENSE RNA C-MYC CELLS PROLIFERATION ANTIBODIES AGE
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
CSHL Authors:	Gilman, Michael Riabowol, Karl
Communities:	CSHL labs
Depositing User:	Matt Covey
Date:	January 1992
Date Deposited:	14 Sep 2015 17:03
Last Modified:	30 Sep 2019 14:44
PMCID:	PMC48195
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/31860

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