NDLI: Transcription factor AP-1 activity is required for initiation of DNA synthesis and is lost during cellular aging.

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Transcription factor AP-1 activity is required for initiation of DNA synthesis and is lost during cellular aging.

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Transcription factor AP-1 activity is required for initiation of DNA synthesis and is lost during cellular aging.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gilman, M. Z. Riabowol, K. Schiff, J.
Description	Author Affiliation: Riabowol K ( Cold Spring Harbor Laboratory, NY 11724.);
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 find 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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Aging Cell Cycle Proto-Oncogene Proteins C-fos Physiology Proto-Oncogene Proteins C-jun Cells, Cultured Growth Substances Pharmacology Isoelectric Point Molecular Sequence Data Oligodeoxyribonucleotides Chemistry Regulatory Sequences, Nucleic Acid Transcription, Genetic Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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