Disease relevance of Atf2

• Phosphorylation and activity of ATF-2 are enhanced dramatically upon serum stimulation of rat chondrosarcoma cells [1].
• In this work we present evidence that v-Myc encoded by the avian retrovirus MC29 stimulates activating transcription factor 2 (ATF2)-dependent transcription [2].
• The total amounts of both CREB and activating transcription factor-2 were not altered in the hippocampus after ischemia [3].
• Similar to axotomy, c-Jun increased and ATF-2 decreased in cultured adult dorsal root ganglion neurons following ultraviolet irradiation [4].
• Persistent phosphorylation of cyclic AMP responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain [3].

Psychiatry related information on Atf2

• Sustained increases in activating transcription factor-2 and activator protein-2 in the rat supraoptic nucleus during water deprivation [5].

High impact information on Atf2

• The activation of JNK in the liver was accompanied by increased phosphorylation of activating transcription factor 2 and followed by an increase in the phosphorylation and level of c-Jun protein, in contrast to no such changes in the brain [6].
• p38 MAPK-mediated transcriptional activation of inducible nitric-oxide synthase in glial cells. Roles of nuclear factors, nuclear factor kappa B, cAMP response element-binding protein, CCAAT/enhancer-binding protein-beta, and activating transcription factor-2 [7].
• Here we show that RA upregulation of PEPCK promoter activity requires the cAMP response element (CRE)-1 in addition to the RA-response element and that activating transcription factor-2 (ATF-2) binds the CRE element to mediate this effect [8].
• Here we demonstrate that the cyclin A gene is a target of ATF-2 in chondrocytes [1].
• Platelet-derived growth factor induces interleukin-6 transcription in osteoblasts through the activator protein-1 complex and activating transcription factor-2 [9].

Chemical compound and disease context of Atf2

• Increases in AP-2 alpha and ATF-2 were sustained throughout the SON during water deprivation, suggesting that these transcription factors could play a role in the maintenance of VP and oxytocin gene transcription in response to dehydration [5].

Biological context of Atf2

• Single IMO elicited rapid induction of c-Fos and phosphorylation of cyclic AMP response element-binding protein (CREB) without changing the expression of early growth response (Egr)1, Fos-related antigen (Fra)-2 or phosphorylated activating transcription factor-2 [10].
• Thus, ATF-2 and c-Jun are deeply involved in amelogenesis and, in particular, ATF2 is related to the proliferation, differentiation, secretion and transition zones [11].
• A cAMP-responsive element-like (CRE-like, TGACGTGA) promoter sequence and a protein kinase A signaling pathway are involved in this induction, and activation of both CRE binding protein (CREB) and activating transcription factor-2 (ATF-2) is required in the above process [12].
• The involvement of p38(MAPK) in the activation of ATF-2, which leads to the transactivation of rat grp78, is confirmed by electrophoretic mobility shift assay using a probe containing the CRE-like sequence as well as by transient transfection assays with a plasmid containing a 710-base pair stretch of the grp78 promoter [12].
• Taken together, our results suggest that v-Myc can affect gene expression indirectly by modulating the activity of ATF2 [2].

Anatomical context of Atf2

• Transient increase in anti-p-ATF2 immunoreactivity in the late secretion ameloblasts apical to the transition zone of rat incisors [11].
• Nuclear ATF-2 was expressed at high levels in apparently all neurons, but not glial cells, throughout the neuraxis except for those neuronal populations which exhibit a high basal level of c-Jun, i.e. dentate gyrus and the motoneurons of cranial and somatosensory neurons [4].
• Following transection of peripheral or central nerve fibres such as optic nerve, medial forebrain bundle, vagal and facial nerve fibres, ATF-2 rapidly decreased in the axotomized neurons during that period when c-Jun was rapidly expressed [4].
• In the enalapril-treated group, JNK-2, p38, phospho-JNK-2, phospho-p38, and ATF-2 protein expressions were significantly increased, and their immunoactivities were strongly detected in the proximal tubular epithelial cells in the cortex, compared with the control group [13].
• This study shows that signaling by target-derived NGF to the cell bodies of sensory neurons consists, in part, of the modulation of levels and activation status of a retrogradely transported transcription factor, ATF2 [14].

Associations of Atf2 with chemical compounds

• Herein, we report that transactivation of grp78, as well as phosphorylation/activation of ATF-2, can be completely annihilated by SB203580, a highly specific inhibitor of p38 mitogen-activated protein kinase (p38(MAPK)) [12].
• A second set of supershift experiments demonstrated that c-Jun, but not activating transcription factor 2, bound to activator protein-1 sites in the promoter of substance P and collagenase genes, but not of the cyclo-oxygenase-2 gene [15].
• Two hours, but not 5 h or 24 h, following systemic application of kainic acid, an increase in SRF was detectable by western blot analysis in hippocampal and cortical homogenates whereas the expression of ATF-2 and CREB did not change [4].
• In contrast, cerivastatin dose-dependently activated the phosphorylation of both c-jun NH2-terminal protein kinase and activating transcription factor-2, and these activations were abolished by the addition of mevalonate [16].

Regulatory relationships of Atf2

• These findings indicate that p38 MAP kinase is functionally regulated not by synthesis but by phosphorylation and regulates the activation of ATF-2 in neurons, and this cascade plays some role in retrograde neuronal reactions [17].

Other interactions of Atf2

• In this study, we investigated the potential involvement of protein kinase C and activating transcription factor-2 in TGF-beta1-induced cardiac hypertrophic responses in cultured neonatal rat ventricular cardiomyocytes [18].
• Our results demonstrate that activation of c-Jun N-terminal kinase 1, phosphorylation of c-Jun and selective occupation of the c-jun promoter by activating transcription factor-2 or c-Jun are part of the neuronal response following excitotoxicity that is considered as the mechanism for neuronal apoptosis in vivo [15].
• Competitive gel shift and supershift assays indicated that Sp2 and Sp3 were bound to an Sp1 site (-40/-31), and activating transcription factor-2 and c-Jun were bound to a CRE site [19].
• RESULT: Treatment of MCs with IL-1 alpha induced a time-dependent increase in JNK1/SAPK kinase activity, assessed by phosphorylation of the activating transcription factor-2 (ATF-2) [20].
• To investigate the neuronal stress signal cascade, activating transcription factor 2 (ATF-2), Fas-ligand (Fas-L) and c-Jun expression and phosphorylation were analyzed by immunohistochemistry [21].

Analytical, diagnostic and therapeutic context of Atf2

• Activating transcription factor 2 (ATF2) was localized in the ameloblasts of rat incisors by immunohistochemistry [11].
• The activation of ATF-2 and c-Jun pathways in the late period of reperfusion in CA1 dying neurons might reflect damage signals in these neurons [22].
• The suppression of ATF-2 and the expression of c-Jun following axotomy and ultraviolet irradiation might be part of a novel neuronal stress response in the brain that strongly resembles the stress response characterized in non-neuronal cells [4].
• Subcutaneous injection of nerve growth factor (NGF) decreased the levels of fast retrograde axonal transport of activated ATF2 by 97% (p < 0.05) and elevated levels of retrograde axonal transport of total ATF2 by twofold (p < 0.02) [14].

References