|
| Status |
Public on Feb 25, 2019 |
| Title |
FoxK1/2 – New Components in Insulin Regulation of Cellular and Mitochondrial Metabolism |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a novel role in the control of apoptosis, metabolism and mitochondrial function.
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| |
|
| Overall design |
RNA-seq of Control, FOXK1 KD, FOXK2 KD, and Double FoxK1/2 knockdown AML12 cell lines with and without insulin stimulation.
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| |
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| Contributor(s) |
Ramirez AK, Sakaguchi M, Kahn CR |
| Citation(s) |
30952843 |
| |
| Submission date |
Feb 13, 2018 |
| Last update date |
Apr 17, 2019 |
| Contact name |
Alfred Ramirez |
| E-mail(s) |
[email protected]
|
| Organization name |
Joslin Diabetes Center
|
| Street address |
One Joslin Place
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (30)
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|
| Relations |
| BioProject |
PRJNA434000 |
| SRA |
SRP132813 |
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