English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

UV light (UV-C) is a potent inducer of thec-fosgene. Cells lacking c-Fos are hypersensitive to the cytotoxic effect of UV-C indicating a protective role ofc-fosinduction. Here we show that cells deficient in c-Fos (fos−/−) are unable to remove cyclobutane pyrimidine dimers (CPDs) from DNA and undergo apoptosis at high frequency via the Fas pathway. We also show that in c-Fos-deficient cells the activation of c-Jun N-terminal kinase (JNK) by UV-C differs from the wild-type (wt, fos+/+). In wt cells JNK activation is transient, returning to control level 5–8 h after treatment, whereas in c-Fos-deficient cells JNK activation was long-lasting and did not return to control level. Inhibition of early JNK activation by the JNK inhibitor SP600125 attenuated CPD repair and increased UV-C induced apoptosis whereas inhibition of late JNK activation attenuated the apoptotic response of c-Fos-deficient cells. Late and sustained activation of JNK resulted in upregulation offas (CD95, apo-1)ligand and induction of caspase 8-dependent apoptosis. The data indicate that the immediate-early induction of the JNK/c-fospathway stimulates the repair of UV-C induced DNA lesions that protects against apoptosis. If this does not occur, cells do not recover from transcription blockage leading, as shown for c-Fos-deficient cells, to a reduced expression of MKP1, sustained JNK activation andfasLoverexpression that finally results in activation of the death receptor pathway. The data support the hypothesis that non-repaired DNA damage is the cause for the late and sustained activation of the MAP kinase pathway in response to genotoxins.

A role for UV-light-induced c-Fos: stimulation of nucleotide excision repair and protection against sustained JNK activation and apoptosis