ATF-4
| Cyclic AMP-dependent transcription factor ATF-4 | ||
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| according to PDB 1CI6 | ||
| other names |
Activating transcription factor 4, Cyclic AMP-responsive element-binding protein 2, CREB-2, cAMP-responsive element-binding protein 2 |
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| Properties of human protein | ||
| Mass / length primary structure | 351 amino acids , 38,590 Da | |
| Identifier | ||
| External IDs | ||
| Orthologue (human) | ||
| Entrez | 468 | |
| Ensemble | ENSG00000128272 | |
| UniProt | P18848 | |
| Refseq (mRNA) | NM_001675.4 | |
| Refseq (protein) | NP_001666.2 | |
| PubMed search |
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Activating transcription factor 4 (ATF 4, CREB 2) is a protein from the group of transcription factors .
properties
As a transcription factor, ATF-4 is a DNA-binding protein . It has a leucine zipper for dimerization . ATF-4 is cAMP -dependent and binds to a DNA sequence , the cAMP response element (CRE) ( consensus sequence : 5'-GTGACGT [AC] [AG] -3 '), which occurs in various cellular and viral promoters . The production of ATF-4 is regulated by the 5 'UTR . In osteoblasts , ATF-4, together with FOXO1, regulates the cell's glucose level by inhibiting the formation of beta cells . In osteoblasts ATF4 regulated together with RUNX2 and osterix the differentiation . The final step in the differentiation of osteoblasts is the mineralization of the extracellular matrix , which is inhibited by inactivation of c-Jun , as the transcription of ATF-4 is consequently reduced.
In the event of cell stress in the endoplasmic reticulum , ATF-4 regulates the induction of DDIT3 / CHOP, asparagine synthetase (ASNS) and NLRP1 . Together with DDIT3 / CHOP, it activates the transcription of TRIB3 and promotes apoptosis in neurons by regulating the transcription of BBC3 / PUMA. In addition, it activates the transcription of SIRT4 . Furthermore, it is in the regulation of circadian rhythm part, by regulating the transcription of Per2 and serotonin - Transporter SLC6A4 . In both genes, ATF-4 binds periodically to the respective CRE. In smooth muscle cells (e.g. in vessels ) ATF-4 is induced by FGF-2 and in turn induces VEGF-A . ATF-4 is phosphorylated . It is produced to a greater extent in the ER under hypoxia .
In HIV , ATF-4 binds to the tax-responsive enhancer element B67 in the LTR .
Pevonedistat induces the transcription of ATF-4.
Web links
Individual evidence
- ↑ Somers J, Pöyry T, Willis AE: A perspective on mammalian upstream open reading frame function . In: Int. J. Biochem. Cell Biol . 45, No. 8, August 2013, pp. 1690-700. doi : 10.1016 / j.biocel.2013.04.020 . PMID 23624144 .
- ^ Franceschi RT, Ge C, Xiao G, Roca H, Jiang D: Transcriptional regulation of osteoblasts . In: Cells, Tissues, Organs . 189, No. 1-4, 2009, pp. 144-52. doi : 10.1159 / 000151747 . PMID 18728356 . PMC 3512205 (free full text).
- ↑ Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T: JNK activity is essential for Atf4 expression and late-stage osteoblast differentiation . In: Journal of Bone and Mineral Research . 24, No. 3, March 2009, pp. 398-410. doi : 10.1359 / jbmr.081107 . PMID 19016586 .
- ↑ MT Chin: ATF-4 and vascular injury: integration of growth factor signaling and the cellular stress response. In: Circulation research. Volume 103, number 4, August 2008, pp. 331-333, doi : 10.1161 / CIRCRESAHA.108.182246 , PMID 18703783 , PMC 2747631 (free full text).
- ^ J. Köditz, J. Nesper, M. Wottawa, DP Stiehl, G. Camenisch, C. Franke, J. Myllyharju, RH Wenger, DM Katschinski: Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor. In: Blood. Volume 110, Number 10, November 2007, pp. 3610-3617, doi : 10.1182 / blood-2007-06-094441 , PMID 17684156 .
- ↑ X. Liu, Y. Jiang, J. Wu, W. Zhang, Y. Liang, L. Jia, J. Yu, LS Jeong, L. Li: NEDD8-activating enzyme inhibitor, MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis through up-regulation of ATF-4. In: Biochemical and biophysical research communications. Volume 488, Number 1, June 2017, pp. 1–5, doi : 10.1016 / j.bbrc.2017.04.122 , PMID 28450112 .