Title | HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Kinet MJ, Malin JA, Abraham MC, Blum ES, Silverman MR, Lu Y, Shaham S |
Journal | Elife |
Volume | 5 |
Date Published | 2016 Mar 08 |
ISSN | 2050-084X |
Keywords | Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Death, Gene Expression Regulation, Developmental, Proteasome Endopeptidase Complex, Signal Transduction, Transcription Factors, Ubiquitin |
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 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. |
DOI | 10.7554/eLife.12821 |
Alternate Journal | Elife |
PubMed ID | 26952214 |
PubMed Central ID | PMC4821803 |
Grant List | P40 OD010440 / OD / NIH HHS / United States HD078703 / HD / NICHD NIH HHS / United States R01 NS081490 / NS / NINDS NIH HHS / United States T32 CA009673 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States R01 HD078703 / HD / NICHD NIH HHS / United States NS081490 / NS / NINDS NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm