The molecular basis for uv response of cultured human cells
During the past year we have analyzed the mechanism by which UV and H{sub 2}O{sub 2} increase the activity of AP-1 in HeLa cells. AP-1 is a dimeric protein complex composed of the fos and jun gene products. After UV irradiation of HeLa cells (or exposure to H{sub 2}O{sub 2}) expression of the c-jun gene rapidly increases at least 50-fold. This induction occurs through the previously identified AP-1 site in the c-jun promoter. This positive autoregulation is mediated by AP-1 complexes that are composed mostly of cJun. cJun is a phosphoprotein that undergoes complex changes in its phosphorylation state following exposure to phorbol esters, growth factors or transforming oncogenes. We show that UV irradiation causes increases in the phosphorylation of cJun. We have been trying to determine the common signal by which DNA damaging agents lead to activation of the UV response. We present evidence that oxidative stress may serve as a signal for AP-1 induction during the UV response. We are also trying to purify and characterize UVIC, a factor secreted from UV damaged cells which protects non-irradiated cells from damage. We have identified UVIC as a 17 kDa polypeptide that retains radioprotective activity after SDS-PAGE and renaturation. We are currently scaling up the isolation and purification process. 4 refs. (MHB)
- Research Organization:
- California Univ., San Diego, La Jolla, CA (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- FG03-86ER60429
- OSTI ID:
- 10104960
- Report Number(s):
- DOE/ER/60429-T1; ON: DE92003766
- Resource Relation:
- Other Information: PBD: [1991]
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ULTRAVIOLET RADIATION
TRANSCRIPTION FACTORS
GENE REGULATION
POST-TRANSLATION MODIFICATION
HELA CELLS
BIOLOGICAL RADIATION EFFECTS
ONCOGENES
RADIOPROTECTIVE SUBSTANCES
PURIFICATION
PROGRESS REPORT
PHOSPHOPROTEINS
BIOLOGICAL STRESS
OXIDATION
560120
RADIATION EFFECTS ON BIOCHEMICALS, CELLS, AND TISSUE CULTURE