DRE-1: an evolutionarily conserved F box protein that regulates C. elegans developmental age.
During metazoan development, cells acquire both positional and temporal identities. The Caenorhabditis elegans heterochronic loci are global regulators of larval temporal fates. Most encode conserved transcriptional and translational factors, which affect stage-appropriate programs in various tissues. Here, we describe dre-1, a heterochronic gene, whose mutant phenotypes include precocious terminal differentiation of epidermal stem cells and altered temporal patterning of gonadal outgrowth. Genetic interactions with other heterochronic loci place dre-1 in the larval-to-adult switch. dre-1 encodes a highly conserved F box protein, suggesting a role in an SCF ubiquitin ligase complex. Accordingly, RNAi knockdown of the C. elegans SKP1-like homolog SKR-1, the cullin CUL-1, and ring finger RBX homologs yielded similar heterochronic phenotypes. DRE-1 and SKR-1 form a complex, as do the human orthologs, hFBXO11 and SKP1, revealing a phyletically ancient interaction. The identification of core components involved in SCF-mediated modification and/or proteolysis suggests an important level of regulation in the heterochronic hierarchy.
Fielenbach
Nicole
N
Baylor College of Medicine, Huffington Center on Aging, Department of Molecular and Cellular Biology, One Baylor Plaza, Houston, TX 77030, USA.
Guardavaccaro
Daniele
D
Neubert
Kerstin
K
Chan
Tammy
T
Li
Dongling
D
Feng
Qin
Q
Hutter
Harald
H
Pagano
Michele
M
Antebi
Adam
A
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D019143:Evolution, Molecular; D044783:F-Box Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; C519094:DRE-1 protein, C elegans; D044783:F-Box Proteins; C479529:RBX1 protein, human; C457579:FBXO11 protein, human; D011484:Protein-Arginine N-Methyltransferases; D044843:SKP Cullin F-Box Protein Ligases; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I