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| Status |
Public on Mar 23, 2012 |
| Title |
A protective strategy against hyperinflammatory responses requiring the non-transcriptional actions of GPS2 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The association between hyper-inflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, non-transcriptional role of GPS2 as a guardian against hyperstimulation of TNFA-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNFA target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the non-transcriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis.
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| Overall design |
RNA-sequencing of polyA selected RNA molecules in 293T cells and ChIP-seq of GPS2, TBL1, and NCOR.
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| Contributor(s) |
Perissi V, Cardamone D, Krones A, Tanasa B, Ricci L, Ohgi KH, Glass CK, Rosenfeld MG |
| Citation(s) |
22424771 |
| Submission date |
Jan 18, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Valentina Perissi |
| E-mail(s) |
vperissi@acs.bu.edu
|
| Phone |
617 638 4115
|
| Fax |
617 638 5339
|
| Organization name |
Boston University School of Medicine
|
| Department |
Department of Biochemistry
|
| Street address |
72 E. Concord St
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (8)
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| Relations |
| SRA |
SRP010430 |
| BioProject |
PRJNA150685 |
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