DAF-16/FOXO requires Protein Phosphatase 4 to initiate transcription of stress resistance and longevity promoting genes
In C. elegans, the conserved transcription factor DAF-16/FOXO is a powerful aging regulator, relaying dire conditions into expression of stress resistance and longevity promoting genes. For some of these functions, including low insulin/IGF signaling (IIS), DAF-16 depends on the protein SMK-1/SMEK,...
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Veröffentlicht in: | NATURE COMMUNICATIONS 2020-01, Vol.11 (1), p.138-138, Article 138 |
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Sprache: | eng |
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Zusammenfassung: | In
C. elegans,
the conserved transcription factor DAF-16/FOXO is a powerful aging regulator, relaying dire conditions into expression of stress resistance and longevity promoting genes. For some of these functions, including low insulin/IGF signaling (IIS), DAF-16 depends on the protein SMK-1/SMEK, but how SMK-1 exerts this role has remained unknown. We show that SMK-1 functions as part of a specific Protein Phosphatase 4 complex (PP4
SMK-1
). Loss of PP4
SMK-1
hinders transcriptional initiation at several DAF-16-activated genes, predominantly by impairing RNA polymerase II recruitment to their promoters. Search for the relevant substrate of PP4
SMK-1
by phosphoproteomics identified the conserved transcriptional regulator SPT-5/SUPT5H, whose knockdown phenocopies the loss of PP4
SMK-1
. Phosphoregulation of SPT-5 is known to control transcriptional events such as elongation and termination. Here we also show that transcription initiating events are influenced by the phosphorylation status of SPT-5, particularly at DAF-16 target genes where transcriptional initiation appears rate limiting, rendering PP4
SMK-1
crucial for many of DAF-16’s physiological roles.
The transcription factor DAF-16/FOXO mediates a wide variety of aging-preventive responses by driving the expression of stress resistance and longevity promoting genes. Here the authors show that transcriptional initiation at many DAF-16/FOXO target genes requires the dephosphorylation of SPT-5 by Protein Phosphatase 4. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-019-13931-7 |