SKN-1 functions in C elegans oxidative stress responses

Joslin Diabetes Center, Boston MA

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Abstract

DESCRIPTION (provided by applicant): Our lab has demonstrated that SKN-1, the transcription factor that specifies the mesoderm fate during early embryogenesis, functions similarly to vertebrate Nrf proteins. SKN-1 accumulates in the intestine nuclei and activates the expression of GCS- 1 in response to different classes of oxidative stress and antioxidants. Besides redox stimuli, SKN-1 is also regulated by GSK-3, DAF-2 and p38 suggesting that this transcription factor might have an essential and global role in the C. elegans oxidant stress defense. In this proposal I will investigate whether arsenite induction of SKN-1 and its target GCS-1 requires also JNK singling and whether sulforaphane induction of SKN-1 and its target GCS-1 requires p38 and/or JNK signaling. I will also identify other genes regulated by SKN-1 using microarrays. And finally, I will investigate whether W02H5.7, an expressed gene highly similar to skn-1, may have parallel or overlapping functions in respect to SKN-1.