RRC ID 53477
著者 Kinet MJ, Malin JA, Abraham MC, Blum ES, Silverman MR, Lu Y, Shaham S.
タイトル HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans.
ジャーナル Elife
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.
巻・号 5
公開日 2016-3-8
DOI 10.7554/eLife.12821
PII e12821
PMID 26952214
PMC PMC4821803
MeSH Animals Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / metabolism* Cell Death* Gene Expression Regulation, Developmental Proteasome Endopeptidase Complex / metabolism* Signal Transduction Transcription Factors / metabolism* Ubiquitin / metabolism*
IF 7.08
引用数 12
リソース情報
線虫 tm2777 tm1968