Deficiency of transcriptional regulator p8 induces autophagy and causes impaired cardiac function
Through autophagy cells adapt to nutrient availability, recycle cellular material and eliminate toxic proteins and damaged cellular organelles. Dysregulation of autophagy is implicated in the pathogenesis of various diseases, including cancer, neurodegeneration and cardiomyopathies. The transcription factor FoxO3 activates autophagy by enhancing the expression of several genes. We find a role for the transcriptional regulator p8 in controling autophagy by repressing FoxO3 transcriptional activity. p8 silencing increases the association of FoxO3 with the bnip3 promoter, a known pro-autophagic FoxO3 target, and results in increasead basal autophagy and decreased cellular viability. Likewise, p8 overexpression inhibits Bnip3 upregulation after autophagy activation. Thus, p8 appears to antagonize the promotion of autophagy mediated by the FoxO3-Bnip3 axis. Consistent with this, bnip3 knockdown restores viability in p8-deficient cells. In vivo, hearts from p8-/- mice have higher basal autophagy and bnip3 levels. These mice develop left ventricular wall thinning and chamber dilation, with consequent impaired cardiac function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Autophagy - 6(2010), 5 vom: 01. Juli, Seite 652-654 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kong, Derek K [VerfasserIn] |
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| Anmerkungen: |
Date Completed 23.08.2017 Date Revised 23.08.2017 published: Print Citation Status PubMed-not-MEDLINE |
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| doi: |
10.4161/auto.6.5.12067 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Deficiency of transcriptional regulator p8 induces autophagy and causes impaired cardiac function |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Through autophagy cells adapt to nutrient availability, recycle cellular material and eliminate toxic proteins and damaged cellular organelles. Dysregulation of autophagy is implicated in the pathogenesis of various diseases, including cancer, neurodegeneration and cardiomyopathies. The transcription factor FoxO3 activates autophagy by enhancing the expression of several genes. We find a role for the transcriptional regulator p8 in controling autophagy by repressing FoxO3 transcriptional activity. p8 silencing increases the association of FoxO3 with the bnip3 promoter, a known pro-autophagic FoxO3 target, and results in increasead basal autophagy and decreased cellular viability. Likewise, p8 overexpression inhibits Bnip3 upregulation after autophagy activation. Thus, p8 appears to antagonize the promotion of autophagy mediated by the FoxO3-Bnip3 axis. Consistent with this, bnip3 knockdown restores viability in p8-deficient cells. In vivo, hearts from p8-/- mice have higher basal autophagy and bnip3 levels. These mice develop left ventricular wall thinning and chamber dilation, with consequent impaired cardiac function | ||
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| 700 | 1 | |a Kyriakis, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Goruppi, Sandro |e verfasserin |4 aut | |
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