| Tbio | Cyclic AMP-dependent transcription factor ATF-4 |
Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to endoplasmic reticulum (ER) stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes. During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors (PubMed:26086088).
This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]
This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]
Comments
Property Summary
| NCBI Gene PubMed Count | 174 |
| Grant Count | 238 |
| R01 Count | 161 |
| Funding | $19,780,708.02 |
| PubMed Score | 529.05 |
| PubTator Score | 303.98 |
| Disease | Z-score | Confidence |
|---|---|---|
| Cancer 2,346 | 4.318 | 2.2 |
| diabetes mellitus 1,663 | 3.371 | 1.7 |
| Obesity 616 | 3.242 | 1.6 |
| Vascular disease 281 | 3.067 | 1.5 |
| Anoxia 33 | ||
| Invasive Ductal Breast Carcinoma 9 | ||
| Necrosis 51 |
| Accession | P18848 Q9UH31 cAMP-dependent transcription factor ATF-4 |
| Symbols |
CREB2 TXREB CREB-2 TAXREB67 |
| PMID | Text |
|---|---|
| 26884600 | The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2alpha. |
| 26771712 | Inhibition or overexpression of ATF4 confirms the role of ATF4 in SESN2 gene up-regulation induced by mitochondrial dysfunction. |
| 26648175 | ATF4 and ATF6beta act synergistically in the negative regulation of placental growth factor mRNA expression |
| 26504039 | Up-regulation of ATF4 is associated with Pancreatic Neuroendocrine Tumors. |
| 26239904 | TBL2 participates in ATF4 translation through its association with the mRNA. |
| 26172539 | a reduction of cell death was associated with decreased levels of ATF4 in a rhabdomyosarcoma cell line |
| 26125799 | Combined administration inhibited the cells most potently and time-dependently, decreased the expression of HO-1, and significantly increased the expression of ATF4, CHOP, and Ire-1 proteins expression levels |
| 26111340 | Global profiling in human mesenchymal stem cells and a novel cell-free assay reveals that ATF4 requires C/EBPbeta for genomic binding at a motif distinct from that bound by the C/EBPbeta homodimer. |
| 26030745 | This study outlines the mechanism of NIR laser phototoxicity and the utility of monitoring surface temperature and ATF4 expression as potential biomarkers to develop safe and effective clinical applications. |
| 26011642 | Upon loss of attachment in tumor cells, ATF4 activated a program of cytoprotective autophagy and antioxidant responses, including induced expression of heme oxygenase 1 (HO-1). Increased levels of HO-1 ameliorated oxidative stress and cell death. |
| More... |
MTEMSFLSSEVLVGDLMSPFDQSGLGAEESLGLLDDYLEVAKHFKPHGFSSDKAKAGSSEWLAVDGLVSP 1 - 70 SNNSKEDAFSGTDWMLEKMDLKEFDLDALLGIDDLETMPDDLLTTLDDTCDLFAPLVQETNKQPPQTVNP 71 - 140 IGHLPESLTKPDQVAPFTFLQPLPLSPGVLSSTPDHSFSLELGSEVDITEGDRKPDYTAYVAMIPQCIKE 141 - 210 EDTPSDNDSGICMSPESYLGSPQHSPSTRGSPNRSLPSPGVLCGSARPKPYDPPGEKMVAAKVKGEKLDK 211 - 280 KLKKMEQNKTAATRYRQKKRAEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEVRKARGKKRV 281 - 350 P//
| PMID | Year | Title |
|---|---|---|
| 26884600 | 2016 | ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2? kinases. |
| 26771712 | 2016 | Mitochondrial dysfunction induces SESN2 gene expression through Activating Transcription Factor 4. |
| 26648175 | 2016 | Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6?: implications for the pathophysiology of human pregnancy complications. |
| 26504039 | 2015 | Endoplasmic Reticulum Stress in Pancreatic Neuroendocrine Tumors is Linked to Clinicopathological Parameters and Possible Epigenetic Regulations. |
| 26239904 | 2016 | TBL2 Associates With ATF4 mRNA Via Its WD40 Domain and Regulates Its Translation During ER Stress. |
| 26172539 | 2015 | ATF4 mediates necrosis induced by glucose deprivation and apoptosis induced by 2-deoxyglucose in the same cells. |
| 26125799 | 2015 | Proapoptotic effects of heme oxygenase-1 inhibitor on Kasumi-1 cells via the ATF4/CHOP/Ire-1? pathway. |
| 26111340 | 2015 | ATF4 licenses C/EBP? activity in human mesenchymal stem cells primed for adipogenesis. |
| 26086088 | 2015 | Transcription Factor ATF4 Induces NLRP1 Inflammasome Expression during Endoplasmic Reticulum Stress. |
| 26030745 | 2015 | Molecular pathway of near-infrared laser phototoxicity involves ATF-4 orchestrated ER stress. |
| More... |
