Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development

Benjamin P. Weaver, Yi M. Weaver, Shohei Mitani, Min Han

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Recent findings suggest that components of the classical cell death machinery also have important non-cell-death (non-apoptotic) functions in flies, nematodes, and mammals. However, the mechanisms for non-canonical caspase substrate recognition and proteolysis, and the direct roles for caspases in gene expression regulation, remain largely unclear. Here we report that CED-3 caspase and the Arg/N-end rule pathway cooperate to inactivate the LIN-28 pluripotency factor in seam cells, a stem-like cell type in Caenorhabditis elegans, thereby ensuring proper temporal cell fate patterning. Importantly, the caspase and the E3 ligase execute this function in a non-additive manner. We show that CED-3 caspase and the E3 ubiquitin ligase UBR-1 form a complex that couples their in vivo activities, allowing for recognition and rapid degradation of LIN-28 and thus facilitating a switch in developmental programs. The interdependence of these proteolytic activities provides a paradigm for non-apoptotic caspase-mediated protein inactivation. The C. elegans caspase CED-3 cleaves the LIN-28 protein to limit its activity during seam cell patterning. Weaver et al. show that this non-apoptotic function of CED-3 occurs in collaboration with a ligase of the Arg/N-end rule pathway, and both proteins are required for efficient recognition and degradation of LIN-28.

Original languageEnglish (US)
Pages (from-to)665-673.e6
JournalDevelopmental Cell
Volume41
Issue number6
DOIs
StatePublished - Jun 19 2017
Externally publishedYes

Keywords

  • Arg/N-end rule
  • developmental timing
  • heterochronic
  • Lin28
  • non-apoptotic
  • proteasome
  • proteostasis
  • stem cell
  • UBR

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development'. Together they form a unique fingerprint.

  • Cite this