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DAF-16/FOXO require...
DAF-16/FOXO requires Protein Phosphatase 4 to initiate transcription of stress resistance and longevity promoting genes
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- Sen, I (författare)
- Karolinska Institutet
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Zhou, X (författare)
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Chernobrovkin, A (författare)
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Puerta-Cavanzo, N (författare)
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- Kanno, T (författare)
- Karolinska Institutet
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- Salignon, J (författare)
- Karolinska Institutet
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Stoehr, A (författare)
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Lin, XX (författare)
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Baskaner, B (författare)
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Brandenburg, S (författare)
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- Bjorkegren, C (författare)
- Karolinska Institutet
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- Zubarev, RA (författare)
- Karolinska Institutet
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- Riedel, CG (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2020-01-09
- 2020
- Engelska.
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 138-
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- 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.
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- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Sen, I
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Zhou, X
-
Chernobrovkin, A
-
Puerta-Cavanzo, ...
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Kanno, T
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Salignon, J
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visa fler...
-
Stoehr, A
-
Lin, XX
-
Baskaner, B
-
Brandenburg, S
-
Bjorkegren, C
-
Zubarev, RA
-
Riedel, CG
-
visa färre...
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Nature communica ...
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Karolinska Institutet