2013 Fiscal Year Final Research Report
N-terminal hydrophobic amino acids of ATF5 protein confer IL-1b-induced stabilization, and responsible for the suppression of the serum amyloid A1 (SAA1) ans SAA2 gene expression
| Project/Area Number |
23590310
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Tokyo University of Pharmacy and Life Science |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Keywords | ATF5 / ストレス / 急性期応答 / 炎症 |
|---|
| Research Abstract |
In this study, we show that IL-1b, a proinflammatory cytokine, increases the expression of ATF5 protein in HepG2 cells in part by stabilizing the ATF5 protein. The N-terminal domain rich in hydrophobic amino acids that is predicted to form a hydrophobic network was responsible for destabilization in steady-state conditions and served as an IL-1b response domain. Furthermore, IL-1b increased the translational efficiency of ATF5 mRNA via the 5' UTR a and phosphorylation of the eukaryotic translation initiation factor 2a (eIF2a). ATF5 knockdown in HepG2 cells up-regulated the IL-1b-induced expression of the serum amyloid A1 (SAA1) and SAA2 genes. Our results show that the N-terminal hydrophobic amino acids play an important role in the regulation of ATF5 protein expression in IL-1b-mediated immune response and that ATF5 is a negative regulator for IL-1b-induced expression of SAA1 and SAA2 in HepG2 cells.
|
Research Products
(13 results)
-
[Journal Article] N-terminal Hydrophobic Amino Acids of Activating Transcription Factor 5 (ATF5) Protein Confer Interleukin 1β(IL-1β)-induced Stabilization2014
Author(s)
Abe T., Kojima M., Akanuma S., Iwashita H., Yamazaki T., Okuyama R., Ichikawa K., Umemura M., Nakano H., Takahashi S., Takahashi Y.
-
Journal Title
J . Biol. Chem
Volume: 289
Pages: 3888-3900
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] The 5'-untranslated region regulates the stability of ATF5mRNA by nonsense-mediated mRNA decay2011
Author(s)
Umemura, M., Hatano, M., Kimura, N., Yamazaki, T., Takeda, H., Nakano, H., Takahashi, S., Takahashi, Y.
Organizer
Cold spring harbor laboratory the 2011 meeting on eukaryotic mRNA processing
Place of Presentation
New York, USA(国内学会発表)
Year and Date
20110800
