TY - JOUR TI - HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans AU - Kinet, Maxime J AU - Malin, Jennifer A AU - Abraham, Mary C AU - Blum, Elyse S AU - Silverman, Melanie R AU - Lu, Yun AU - Shaham, Shai A2 - Hobert, Oliver VL - 5 PY - 2016 DA - 2016/03/08 SP - e12821 C1 - eLife 2016;5:e12821 DO - 10.7554/eLife.12821 UR - https://doi.org/10.7554/eLife.12821 AB - 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 have been molecularly characterized, none appear to control developmental cell culling. Linker-cell-type death (LCD) is a morphologically conserved non-apoptotic cell death process operating in Caenorhabditis elegans and vertebrate development, and is therefore a compelling candidate process complementing apoptosis. However, the 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 mitogen-activated protein kinase kinase signaling control heat shock factor 1 (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, BTBD-2, and SIAH-1. Our studies uncover design similarities between LCD and developmental apoptosis, and provide testable predictions for analyzing LCD in vertebrates. KW - linker cell death KW - hsf-1 KW - UPS KW - BTBD2 KW - UBE2D2 KW - let-70 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -