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| RADIATION SIGNALING MEDIATED BY JUN ACTIVATION FOLLOWING DISSOCIATION FROM A CELL TYPE-SPECIFIC REPRESSOR |
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| Author(s): HALLAHAN DE, GIUS D, KUCHIBHOTLA J, SUKHATME V, KUFE DW, WEICHSELBAUM RR |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 268 Issue: 7 Pages: 4903-4907 Published: MAR 5 1993 |
| Times Cited: 48 References: 33 |
| Abstract: The promoter regions of several radiation-inducible genes contain AP-1 cis-acting regulatory elements that are dependent upon protein kinase C signaling. We analyzed nuclear protein from irradiated human tumor cell lines for binding to the AP-1 consensus sequence. The increase in nuclear protein binding following irradiation was specific for the AP-1 sequence and was reduced by antibodies to c-Jun and c-Fos. The AP-1 DNA binding sequence was found to regulate transcription in irradiated cells and mutation of the AP-1 site within the c-jun promoter abolished transcriptional induction by radiation. The gene encoding the chimeric transcription factor Gal4-Jun5-253, which includes the DNA binding region of Gal4 and the transcriptional regulatory region of c-Jun, was cotransfected with the reporter plasmid with Gal4 binding sequences (G5B-CAT). Transfection of RIT-3 and HeLa cells revealed that the regulatory region of Jun was sufficient to activate transcription following irradiation. Conversely, Hep G2 cells, which do not contain the cell type-specific Jun repressor, were not responsive to radiation-induced Jun activation. The c-Jun repressor was found to regulate Jun activation by experiments using the expression vector CMV-jun, which competes for Jun inhibitor and eliminates radiation-induction of Jun. We propose transcription factor dissociation from inhibitor proteins may participate in the initiation of cellular responses to ionizing radiation. |
| Document Type: Article |
| Language: English |
| Reprint Address: HALLAHAN, DE (reprint author), UNIV CHICAGO, DEPT RADIAT & CELLULAR ONCOL, 5841 S MARYLAND AVE, BOX 442, CHICAGO, IL 60637 USA |
Addresses:
1. MICHAEL REESE MED CTR, DEPT RADIAT & CELLULAR ONCOL, CHICAGO, IL 60637 USA
2. UNIV CHICAGO, DEPT MED, CHICAGO, IL 60637 USA
3. UNIV CHICAGO, DEPT MOLEC GENET, CHICAGO, IL 60637 USA
4. UNIV CHICAGO, DEPT CELL BIOL, CHICAGO, IL 60637 USA
5. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, CLIN PHARMACOL LAB, BOSTON, MA 02115 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: KP884 |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |