Coordinated inhibition of C/EBP by Tribbles in multiple tissues is essential for Caenorhabditis elegans development.
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nipi-3 null mutants arrest at L2-L3 and die within 5-10 days
"Mutants arrested development at the second to third larval stages (L2-L3) (see below) and eventually died between 5-10 days after hatching."
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NIPI-3 physically interacts with CEBP-1 via yeast two-hybrid
"One prominent candidate interacting partner was CEBP-1, a member of the C/EBP family of transcription factors"
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Loss of cebp-1 completely suppresses nipi-3 null lethality
"Remarkably, cebp-1(0) completely suppressed the growth and fertility defects of nipi-3(0) mutants"
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NIPI-3 represses cebp-1 transcription in multiple tissues
"Strikingly, the expression of the cebp-1 transcriptional reporter was highly and significantly increased in both nipi-3(fr4) and nipi-3(0) mutants, compared with wild-type animals"
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NIPI-3 localizes predominantly to nuclei in epidermis, intestine, and neurons
"GFP::NIPI-3 expression was observed predominantly in the nuclei (Fig. 1i), with an overall intensity peaking at the L2-L3 stages."
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NIPI-3 negatively modulates PMK-1 phosphorylation via CEBP-1
"levels of active PMK-1 were significantly increased in nipi-3(0), but remained similar to wild type in cebp-1(0) and cebp-1(0) nipi-3(0) animals"
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Loss of PMK-1 pathway components also suppresses nipi-3 null lethality
"Among the other suppressors of nipi-3(0), we found missense alterations in TIR-1/the sterile alpha (SAM) and Toll-interleukin receptor (TIR) motif-containing protein SARM), NSY-1/MAPKKK, SEK-1/MAPKK and MAK-2/MAPK-activated protein kinase (MAPKAPK)"