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

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 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, BTBD2, and SIAH-1. Our studies uncover design similarities between LCD and developmental apoptosis, and provide testable predictions for analyzing LCD in vertebrates.

Article and author information

Author details

  1. Maxime J Kinet

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jennifer A Malin

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mary C Abraham

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Elyse S Blum

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Melanie R Silverman

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yun Lu

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. 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.

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: November 4, 2015
  2. Accepted: March 7, 2016
  3. Accepted Manuscript published: March 8, 2016 (version 1)
  4. Accepted Manuscript updated: March 9, 2016 (version 2)
  5. Version of Record published: March 30, 2016 (version 3)

Copyright

© 2016, Kinet et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Maxime J Kinet
  2. Jennifer A Malin
  3. Mary C Abraham
  4. Elyse S Blum
  5. Melanie R Silverman
  6. Yun Lu
  7. Shai Shaham
(2016)
HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans
eLife 5:e12821.
https://doi.org/10.7554/eLife.12821
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