LIN-3/EGF Promotes the Programmed Cell Death of Specific Cells in by Transcriptional Activation of the Pro-apoptotic Gene

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Programmed cell death (PCD) is an evolutionarily conserved cellular process that is important for metazoan development and homeostasis. The epidermal growth factor (EGF) promotes cell proliferation, differentiation and survival during animal development. Surprisingly, we found that the EGF-like ligand LIN-3 also promotes the death of specific cells in Caenorhabditis elegans. We found that the LIN-3/EGF signal can be secreted from a cell to facilitate the demise of cells at a distance by activating the transcription of the PCD-promoting gene egl-1 in the doomed cells through the transcription factor LIN-1. LIN-1 binds to the egl-1 promoter in vitro and is positively regulated by the LIN-3/EGF, LET-23/EGF receptor, and the downstream MAPK signaling pathway. To our knowledge, LIN-3/EGF is the first extrinsic signal that has been shown to regulate the intrinsic PCD machinery during C. elegans development. In addition, the transcription factor LIN-31, which binds to LIN-1 and acts downstream of LIN-3/EGF, LET-23/EGF receptor, and the MAPK signaling pathway during vulval development, is dispensable for PCD. Thus, LIN-3/EGF promotes cell proliferation, differentiation, and PCD through common downstream signaling molecules but acts via distinct sets of transcription factors for different target gene expression.

Vyšlo v časopise: LIN-3/EGF Promotes the Programmed Cell Death of Specific Cells in by Transcriptional Activation of the Pro-apoptotic Gene. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004513
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004513

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