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

Journal Article · Wed Jan 01 04:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.89.1.157· OSTI ID:5618022

Riabowol, K; Schiff, J; Gilman, M Z ^[1]

---

1. Cold Spring Harbor Lab., NY (United States)

Activation of the AP-1 complex of transcription factors is one of the earliest nuclear responses to mitogenic stimuli. The authors demonstrate directly that AP-1 activity is required for human cells to proliferate in response to serum. They 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.

• OSTI ID: 5618022
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 89:1; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
CARBOXYLIC ACIDS
CELL PROLIFERATION
CHEMISTRY
CONNECTIVE TISSUE CELLS
CYTOCHEMISTRY
DAYS LIVING RADIOISOTOPES
DNA REPLICATION
DRUGS
ENZYME ACTIVITY
EVEN-ODD NUCLEI
FIBROBLASTS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
MAN
MEMBRANE PROTEINS
METABOLIC ACTIVATION
METHIONINE
MOLECULAR BIOLOGY
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEOPROTEINS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
RECEPTORS
SOMATIC CELLS
SULFUR 35
SULFUR ISOTOPES
TRANSCRIPTION FACTORS
VERTEBRATES