| 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
|
| Resource |
| C.elegans |
tm2993
tm1445 |
