title: Control of nonapoptotic developmental cell death in Caenorhabditis elegans by a polyglutamine-repeat protein.
abstract: Death is a vital developmental cell fate. In Caenorhabditis elegans, programmed death of the linker cell, which leads gonadal elongation, proceeds independently of caspases and apoptotic effectors. To identify genes promoting linker-cell death, we performed a genome-wide RNA interference screen. We show that linker-cell death requires the gene pqn-41, encoding an endogenous polyglutamine-repeat protein. pqn-41 functions cell-autonomously and is expressed at the onset of linker-cell death. pqn-41 expression is controlled by the mitogen-activated protein kinase kinase SEK-1, which functions in parallel to the zinc-finger protein LIN-29 to promote cellular demise. Linker-cell death is morphologically similar to cell death associated with normal vertebrate development and polyglutamine-induced neurodegeneration. Our results may therefore provide molecular inroads to understanding nonapoptotic cell death in metazoan development and disease.
authors.affiliation: Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Elyse S
authors.initials: ES
authors.lastname: Blum
authors.forename: Mary C
authors.initials: MC
authors.lastname: Abraham
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.forename: Shai
authors.initials: S
authors.lastname: Shaham
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016923:Cell Death; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D049751:Genome, Helminth; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C095571:LIN-29 protein, C elegans; D050505:Mutant Proteins; C570598:PQN-41 protein, C elegans; D010455:Peptides; D014157:Transcription Factors; C097188:polyglutamine; D048670:MAP Kinase Kinase 4; C516679:sek-1 protein, C elegans