RRC ID 53308
著者 Malin JA, Kinet MJ, Abraham MC, Blum ES, Shaham S.
タイトル Transcriptional control of non-apoptotic developmental cell death in C. elegans.
ジャーナル Cell Death Differ
Abstract Programmed cell death is an essential aspect of animal development. Mutations in vertebrate genes that mediate apoptosis only mildly perturb development, suggesting that other cell death modes likely have important roles. Linker cell-type death (LCD) is a morphologically conserved cell death form operating during the development of Caenorhabditis elegans and vertebrates. We recently described a molecular network governing LCD in C. elegans, delineating a key role for the transcription factor heat-shock factor 1 (HSF-1). Although HSF-1 functions to protect cells from stress in many settings by inducing expression of protein folding chaperones, it promotes LCD by inducing expression of the conserved E2 ubiquitin-conjugating enzyme LET-70/UBE2D2, which is not induced by stress. Following whole-genome RNA interference and candidate gene screens, we identified and characterized four conserved regulators required for LCD. Here we show that two of these, NOB-1/Hox and EOR-1/PLZF, act upstream of HSF-1, in the context of Wnt signaling. A third protein, NHR-67/TLX/NR2E1, also functions upstream of HSF-1, and has a separate activity that prevents precocious expression of HSF-1 transcriptional targets. We demonstrate that the SET-16/mixed lineage leukemia 3/4 (MLL3/4) chromatin regulation complex functions at the same step or downstream of HSF-1 to control LET-70/UBE2D2 expression. Our results identify conserved proteins governing LCD, and demonstrate that transcriptional regulators influence this process at multiple levels.
巻・号 23(12)
ページ 1985-1994
公開日 2016-12-1
DOI 10.1038/cdd.2016.77
PII cdd201677
PMID 27472063
PMC PMC5136488
MeSH Animals Apoptosis / genetics* Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / metabolism Models, Biological Transcription, Genetic* Wnt Signaling Pathway / genetics
IF 10.717
引用数 6
リソース情報
線虫 tm1968