Reference - Detail
| RRC ID | 59590 |
|---|---|
| Author | Sen I, Zhou X, Chernobrovkin A, Puerta-Cavanzo N, Kanno T, Salignon J, Stoehr A, Lin XX, Baskaner B, Brandenburg S, Björkegren C, Zubarev RA, Riedel CG. |
| Title | DAF-16/FOXO requires Protein Phosphatase 4 to initiate transcription of stress resistance and longevity promoting genes. |
| Journal | Nat Commun |
| Abstract |
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 (PP4SMK-1). Loss of PP4SMK-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 PP4SMK-1 by phosphoproteomics identified the conserved transcriptional regulator SPT-5/SUPT5H, whose knockdown phenocopies the loss of PP4SMK-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 PP4SMK-1 crucial for many of DAF-16's physiological roles. |
| Volume | 11(1) |
| Pages | 138 |
| Published | 2020-1-9 |
| DOI | 10.1038/s41467-019-13931-7 |
| PII | 10.1038/s41467-019-13931-7 |
| PMID | 31919361 |
| PMC | PMC6952425 |
| MeSH | Aging / genetics Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* Forkhead Transcription Factors / genetics* Gene Expression Regulation / genetics* Longevity / genetics Multiprotein Complexes / metabolism Phosphoprotein Phosphatases / genetics* Phosphoprotein Phosphatases / metabolism* RNA Interference RNA Polymerase II / metabolism Stress, Physiological / genetics Transcription, Genetic / genetics Transcriptional Elongation Factors / genetics Transcriptional Elongation Factors / metabolism* |
| IF | 11.878 |
| Times Cited | 0 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 12 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2993 tm1445 |