HSF-1 activates the ubiquitin proteasome system to promote non-ppoptotic developmental cell death in C. elegans

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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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Maxime J Kinet

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Jennifer A Malin

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Mary C Abraham

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Elyse S Blum

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Melanie R Silverman

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Yun Lu

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Shai Shaham

Laboratory of Developmental Genetics, The Rockefeller University, New York, United States

For correspondence
shaham@rockefeller.edu

Competing interests
The authors declare that no competing interests exist.

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