RRC ID 51410
Author Weaver BP, Weaver YM, Mitani S, Han M.
Title Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development.
Journal Dev Cell
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.
Volume 41(6)
Pages 665-673.e6
Published 2017-6-19
DOI 10.1016/j.devcel.2017.05.013
PII S1534-5807(17)30395-7
PMID 28602583
PMC PMC5521180
MeSH Animals Apoptosis / physiology Caenorhabditis elegans / embryology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Caspases / metabolism* Cell Differentiation / physiology* Embryonic Development / genetics* Gene Expression Regulation, Developmental / physiology* Proteolysis RNA-Binding Proteins / metabolism* Signal Transduction / physiology Ubiquitin-Protein Ligases / metabolism
IF 9.19
Times Cited 19
Resource
C.elegans tm5996