HSF-1 activates the ubiquitin proteasome system to promote non-ppoptotic developmental cell death in C. elegans
- The Rockefeller University, United States
Abstract
Apoptosis is a prominent metazoan cell death form. Yet, mutations in apoptosis regulators cause only minor defects in vertebrate development, suggesting that another developmental cell death mechanism exists. While some non-apoptotic programs are characterized, none appear to control developmental cell-culling. Linker-cell-type death (LCD) is a morphologically conserved non-apoptotic cell death process operating in C. elegans and vertebrate development, and is therefore a compelling candidate-process complementing apoptosis. However, details of LCD execution are not known. Here we delineate a molecular-genetic pathway governing LCD in C. elegans. Redundant activities of antagonistic Wnt signals, a temporal-control pathway, and MAPKK signaling control HSF-1, a conserved stress-activated transcription factor. Rather than protecting cells, HSF-1 promotes their demise by activating components of the ubiquitin-proteasome-system, including the E2-ligase LET-70/UBE2D2 functioning with E3 components CUL-3, RBX-1, TAG-30/BTBD2, and SIAH-1. Our studies uncover design similarities between LCD and developmental apoptosis, and provide testable predictions for analyzing LCD in vertebrates.
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© 2016, Kinet et al.
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HSF-1 activates the ubiquitin proteasome system to promote non-ppoptotic developmental cell death in C. elegans
eLife 5:e12821.
https://doi.org/10.7554/eLife.12821
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