HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans.
Elife
; 52016 Mar 08.
Article
en En
| MEDLINE
| ID: mdl-26952214
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Muerte Celular
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Ubiquitina
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Complejo de la Endopetidasa Proteasomal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos