Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CREB”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2001

CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium.

The regulatory influences of glycogen synthase kinase-3 beta (GSK3 beta) and lithium on the activity of cyclic AMP response element binding protein (CREB) were examined in human neuroblastoma SH-SY5Y cells. Activation of Akt (protein kinase B) with serum-increased phospho-serine-9-GSK3 beta (the inactive form of the enzyme), inhibited GSK3 beta activity, and increased CREB DNA binding activity. Inhibition of GSK3 beta by another paradigm, treatment with the selective inhibitor lithium, also increased CREB DNA binding activity. The inhibitory regulation of CREB DNA binding activity by GSK3 beta also was evident in differentiated SH-SY5Y cells, indicating that this regulatory interaction is maintained in non-proliferating cells. These results demonstrate that inhibition of GSK3 beta by serine-9 phosphorylation or directly by lithium increases CREB activation. Conversely, overexpression of active GSK3 beta to 3.5-fold the normal levels completely blocked increases in CREB DNA binding activity induced by epidermal growth factor, insulin-like growth factor-1, forskolin, and cyclic AMP. The inhibitory effects due to overexpressed GSK3 beta were reversed by treatment with lithium and with another GSK 3beta inhibitor, sodium valproate. Overall, these results demonstrate that GSK3 beta inhibits, and lithium enhances, CREB activation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2003

Opposite regulation by typical and atypical anti-psychotics of ERK1/2, CREB and Elk-1 phosphorylation in mouse dorsal striatum.

The two mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), are involved in the control of gene expression via phosphorylation and activation of the transcription factors cyclic AMP response element binding protein (CREB) and Elk-1. Here, we have examined the effect of haloperidol and clozapine, two anti-psychotic drugs, and eticlopride, a selective dopamine D2 receptor antagonist, on the state of phosphorylation of ERK1/2, CREB and Elk-1, in the mouse dorsal striatum. Administration of the typical anti-psychotic haloperidol stimulated the phosphorylation of ERK1/2, CREB and Elk-1. Virtually identical results were obtained using eticlopride. In contrast, the atypical anti-psychotic clozapine reduced ERK1/2, CREB and Elk-1 phosphorylation. This opposite regulation was specifically exerted by haloperidol and clozapine on ERK, CREB, and Elk-1 phosphorylation, as both anti-psychotic drugs increased the phosphorylation of the dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) at the cyclic AMP-dependent protein kinase (PKA) site. The activation of CREB and Elk-1 induced by haloperidol appeared to be achieved via different signalling pathways, as inhibition of ERK1/2 activation abolished the stimulation of Elk-1 phosphorylation without affecting CREB phosphorylation. This study shows that haloperidol and clozapine induce distinct patterns of phosphorylation in the dorsal striatum. The results provide a novel biochemical paradigm elucidating the molecular mechanisms underlying the distinct therapeutic actions of typical and atypical anti-psychotic agents.

Animals↗
PubMed2003

Dopamine-dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum.

Chronic morphine leads to compensatory up-regulation of cAMP signaling pathways in numerous brain regions. One potential consequence of up-regulated cAMP signaling is increased phosphorylation of cAMP response element binding protein (CREB), a transcription factor that may regulate neuroadaptations related to morphine dependence. Altered gene expression within the nucleus accumbens (NAc), a ventral component of the striatum that receives substantial dopaminergic input, may play a role in some of the motivational aspects of opiate withdrawal. To determine if morphine withdrawal leads to increased CREB phosphorylation in striatal tissues, we examined the effects of naloxone-precipitated morphine withdrawal on CREB phosphorylation in primary cultures of rat striatal neurons. Precipitated morphine withdrawal was associated with enhanced dopamine-, SKF 82958 (D1 receptor agonist)-, and forskolin-induced CREB phosphorylation. During precipitated withdrawal, D1 receptor-mediated CREB phosphorylation was dependent on cAMP-dependent protein kinase (PKA). Precipitated withdrawal also led to up-regulation of c-fos mRNA in response to SKF 82958. CREB protein levels were not altered by acute or chronic morphine. These results suggest that D1 receptor-mediated signal transduction is enhanced during morphine withdrawal. Furthermore, they are consistent with in vivo evidence suggesting that increased CREB activation in portions of the striatum (e.g. the NAc) is related to dysphoric states associated with drug withdrawal.

Animals↗
PubMed1994

Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors.

The cAMP response element binding protein (CREB) has been implicated as a key regulator in the transcriptional control of many genes. To assess the functional importance of CREB in vivo and its role in development, we used gene targeting to generate mice with a disruption of the CREB gene. Homozygous mutant mice appeared healthy and exhibited no impairment of growth or development. In this report we demonstrate that CREB and two other members of the CREB/ATF family, cAMP response element modulation protein (CREM) and activating transcription factor 1 (ATF1), appear to form a unique subgroup within this extensive class of transcription factors. Examination of CREM mRNA and protein levels in CREB mutant mice demonstrated overexpression of CREM in all tissues examined, but no change in ATF1 levels. These data demonstrate that CREB is not the sole mediator of cAMP-dependent transcriptional regulation and probably acts in concert with a specific subset of cAMP response element-binding proteins to transduce the cAMP signal and, in its absence, these same proteins can compensate for CREB function in vivo.

Activating Transcription Factor 1↗
PubMed2000

Distinct cAMP response element-binding protein (CREB) domains stimulate different steps in a concerted mechanism of transcription activation.

Hormones and neurotransmitters rapidly change patterns of gene expression in target cells by activating protein kinases that phosphorylate and modify the activity of CREB and other transcription factors. Although CREB was initially characterized as mediating the response to cAMP, CREB phosphorylation and activation are stimulated by diverse extracellular signals and protein kinases in essentially all cells and tissues. CREB stimulates transcription through a constitutive activation domain (CAD), which interacts with the promoter recognition factor TFIID, and through a kinase-inducible domain (KID), when Ser-133 is phosphorylated. The present study provides new insight into the mechanism of activation by showing that each of the CREB domains contributes to transcription initiation by stimulating sequential steps in the transcription reaction. The CAD effectively assembled a polymerase complex, as evidenced by constitutive activation in vivo and stimulation of single-round transcription in vitro. In contrast, phosphorylation of the KID in CREB stimulated isomerization of the polymerase complex, as determined by abortive initiation, and promoter clearance and/or reinitiation, as measured by multiple rounds of transcription. Our results provide evidence for a new model for CREB-mediated induction through a concerted mechanism involving establishment of a polymerase complex by the CAD, followed by stimulation of isomerization, promoter clearance, and/or reinitiation by phosphorylated KID to enhance target gene transcription.

Cell Line↗
PubMed2002

Salt-inducible kinase represses cAMP-dependent protein kinase-mediated activation of human cholesterol side chain cleavage cytochrome P450 promoter through the CREB basic leucine zipper domain.

Salt-inducible kinase (SIK), one of the serine/threonine protein kinases, was transiently expressed in Y1 cells during the early phase of the ACTH/cAMP-dependent protein kinase (PKA)-mediated signal transduction. The overexpression of SIK(N), the SIK's N-terminal kinase domain, repressed the expression of the side chain cleavage cytochrome P450 (CYP11A) gene. To elucidate the mechanism of the repression by SIK, several CYP11A promoter constructs were tested for the promoter activities in the presence of PKA and/or SIK(N). A cAMP-response element (CRE)-like sequence present in the promoter was shown to be responsible not only for the PKA-mediated promoter activation but also for the SIK(N)-mediated repression. When the Gal4 DNA binding domain-linked full-length CRE-binding protein (CREB) construct was cotransfected with Gal4 reporter gene, SIK(N) repressed the PKA-induced reporter gene expression. However, SIK(N) could not repress the PKA-induced reporter activity conferred by Gal4 DNA binding domain-linked basic leucine zipper (bZIP)-less CREB or bZIP-disrupted CREB. On the other hand, SIK(N) could repress the kinase-inducible domain-disrupted CREB-dependent reporter gene expression in the presence of PKA. The in vitro kinase reaction studies showed that SIK(N) could not phosphorylate CREB, and PKA failed to phosphorylate SIK(N). Taken together, these results suggest that SIK(N), cooperating with PKA, may act on the CREB's bZIP domain and repress the CREB-mediated transcriptional activation of the CYP11A gene.

Base Sequence↗
PubMed2002

Nitric oxide protects neuroblastoma cells from apoptosis induced by serum deprivation through cAMP-response element-binding protein (CREB) activation.

The transcription factor cAMP-response element-binding protein (CREB) mediates survival in many cells, including neurons. Recently, death of cerebellar granule neurons due to nitric oxide (NO) deprivation was shown to be accompanied by down-regulation of CREB activity (). We now provide evidence that overproduction of endogenous NO or supplementation with exogenous NO renders SK-N-BE human neuroblastoma cells more resistant to apoptosis induced by serum deprivation. Parental cells underwent apoptosis after 24 h of serum deprivation, an outcome largely absent in clones overexpressing human neuronal nitric oxide synthase (nNOS). This protective effect was reversed by the inhibition of NOS itself or soluble guanylyl cyclase, pointing at cGMP as an intermediate effector of NO-mediated rescue. A slow-releasing NO donor protected parental cells to a significant extent, thus confirming the survival effect of NO. The impaired viability of serum-deprived parental cells was accompanied by a strong decrease of CREB phosphorylation and transcriptional activity, effects significantly attenuated in nNOS-overexpressing clones. To confirm the role of CREB in survival, the ectopic expression of CREB and/or protein kinase A largely counteracted serum deprivation-induced cell death of SK-N-BE cells, whereas transfection with a CREB negative mutant was ineffective. These experiments indicate that CREB activity is an important step for NO-mediated survival in neuronal cells.

Apoptosis↗
PubMed1993

Isolation of Drosophila CREB-B: a novel CRE-binding protein.

CREB is a DNA-binding protein that stimulates gene transcription upon activation of the cAMP signaling pathway. The mammalian CREB protein consists of an amino-terminal transcriptional activation domain and a carboxy-terminal DNA-binding domain comprised of a basic region and a leucine zipper. Recent studies have shown that the mammalian CREB is one of many transcription factors that can bind to the cAMP regulated enhancer (CRE) sequence. Consequently, a complete understanding of regulation through the CRE sequence requires the elucidation of how the various CRE-binding proteins interact with each other. To accomplish this goal, we have begun to characterize the family of CRE-binding proteins in a system that is amenable to genetic manipulations, Drosophila melanogaster. We have previously cloned a protein designated dCREB-A from a Drosophila embryonic cDNA library. Here, we describe an additional member of the Drosophila CREB gene family, isolated by screening a lambda gt11 library of adult Drosophila head cDNAs with a multimerized CRE sequence. This protein, dCREB-B, contains 285 amino acids and is remarkably similar within the basic/zipper region to the corresponding portion of mammalian CREB. In contrast, the dCREB-B and mammalian CREB zipper domains differ considerably from the dCREB-A zipper in both length and composition. However, the putative DNA binding domains for all three proteins are highly conserved. The activator region of dCREB-B is completely different from that of both mammalian CREB and dCREB-A. Northern blot analysis shows that multiple transcripts of the dCREB-B gene are expressed in embryonic and adult tissues and that these transcripts arise from both strands of the DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2004

Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro: activation of CREB downstream of GSK3beta.

In vivo, left ventricular remodeling after myocardial infarction involves hypertrophy generally attributed to increased cardiac workload. We hypothesized that hypoxia/reoxygenation directly induces cardiomyocyte hypertrophy and studied several participating kinases and transcription factors in isolated cardiomyocytes. Hypoxia for 6 h followed by 42 h reoxygenation induced cardiomyocyte hypertrophy assessed by 3H leucine incorporation and immunohistochemistry. Inhibition of reactive oxygen species (ROS), serine/threonine kinase AKT, and ERK abolished reoxygenation-induced hypertrophy. In addition, a beta2-adrenergic receptor (beta2-AR) antagonist, as well as Gi inhibitor pertussis toxin, blocked reoxygenation-induced hypertrophy. Hypoxia for 6 h increased transcription factors CREB, NF-kappaB, and GATA DNA binding activities. However, only CREB DNA-binding was sustained during reoxygenation. Inhibition of PI3-kinase, ERK, and PKA abrogated reoxygenation-induced CREB DNA-binding without affecting CREB serine-133 phosphorylation. These same pathways were found to regulate hypoxia/reoxygenation-induced GSK3beta kinase activity and CREB serine-129 de-phosphorylation. GSK3beta mutants resistant to phosphorylation blocked the stimulation of CRE-dependent transcription induced by hypoxia/reoxygenation. Transfection of cardiomyocytes with a dominant-negative mutant of CREB abrogated hypoxia/reoxygenation-induced hypertrophy. We suggest that hypoxia/reoxygenation induces cardiomyocyte hypertrophy through CREB activation. Inactivation of GSK3beta by hypoxia/reoxygenation, possibly integrating PI3-kinase and ERK pathways downstream of beta2-AR and ROS, is a prerequisite for CRE-dependent transcription. Transient hypoxia may contribute to cardiac hypertrophy in ischemic heart disease independent of cardiac workload.

Adrenergic beta-Antagonists↗
PubMed2002

Localization and functional investigation of the transcription factor CREB in taste receptor cells.

Taste receptor cells utilize the cAMP and other second messenger systems in transducing sweet and bitter stimuli into physiological responses. However, long-term consequences of taste stimulation, such as gene expression, are unknown. We investigated the presence of cAMP response element-binding protein (CREB), a stimulus-induced transcription factor, in taste receptor cells. Using immunocytochemistry, both CREB and its activated form, phosphorylated-CREB (pCREB), were localized to a subset of rat taste receptor cells. Basal level of pCREB was high in the absence of any known stimulation. Using western blot analysis and specific protein kinase inhibitors, CREB phosphorylation was demonstrated to be linked to protein kinase A but not to protein kinase C activation. Stimulation of taste receptor cells with sucrose, a sweet stimulus that elevates cAMP levels, was without effect on CREB phosphorylation. There was a tendency for quinine stimulation, a bitter stimulus that lowers cAMP, to reduce CREB phosphorylation. These results suggested that taste receptor cells express CREB and that its phosphorylation is influenced by the cAMP second messenger system.

Animals↗
PubMed2004

Adenoviral expression of CREB protects neurons from apoptotic and excitotoxic stress.

In this study we have used a molecular approach to manipulate CREB gene expression to study its role in the regulation of neuronal cell death. To achieve this, adenoviral (Ad) vectors encoding EGFP, CREB, and a powerful CREB dominant-negative, known as A-CREB were constructed. The over-expression of CREB but not A-CREB was found to protect primary hippocampal neurons from staurosporine-induced apoptosis, glutamate induced excitotoxicity and exposure to an in vitro ischaemic stress. Hence, manipulating CREB-regulated pathways may provide a means of delaying or preventing the neuronal cell death associated with ischaemic related injury, and in neurodegenerative diseases such as Huntington's and Alzheimer's disease.

Adenoviridae↗
PubMed2004

CREB deficient mice show inhibition and low activity in novel environments without changes in stress reactivity.

The ability to respond to unexpected or novel stimuli is critical for survival. Determining that a stimulus is indeed novel requires memory to ascertain its lack of familiarity. As the long-term synaptic changes involved in memory formation require the cAMP response element binding protein (CREB), we examined the extent to which CREB is involved in responses to novel environments. These environments typically trigger an endocrine stress response. Thus, we measured behavioural and stress hormone responses to three novel and one familiar environment in mice with a targeted disruption of the alpha and delta isoforms of the CREB gene (CREB(alphadelta-) deficient mice). We found CREB(alphadelta-) deficient mice to be less active and more inhibited in the elevated plus maze, open field, and light/dark box, without showing differences in anxiety-like behaviour. This inhibition is unique to novel environments because these mice display a normal phenotype in the home cage, a familiar environment. Although CREB(alphadelta-) deficient mice exhibit altered behaviour in novel environments, they show normal reactivity to mild and moderate stress as both basal and stress levels of corticosterone are similar to those of wild-type controls. This is the first report of CREB(alphadelta-) deficient mice to: (i) show altered behaviour, not related to learning and memory-associated behaviours, upon initial exposure to environments and (ii) serve as an animal model that can dissociate locomotor activity from anxiety-like behaviour in novel environments.

Animals↗
PubMed2006

Striatal modulation of cAMP-response-element-binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease.

Recent evidence has shown that the activity of cAMP responsive element-binding protein (CREB) and of CREB-binding protein (CBP) is decreased in Huntington's disease (HD) [Steffan et al. (2000)Proc. Natl Acad. Sci. USA, 97, 6763-6768; Gines et al. (2003)Hum. Mol. Genet., 12, 497-508; Rouaux et al. (2004) Biochem. Pharmacol., 68, 1157-1164; Sugars et al. (2004)J. Biol. Chem., 279, 4988-4999]. Such decrease is thought to reflect the impaired energy metabolism observed in a HD mouse model, where a decline in striatum cAMP levels has been observed [Gines et al. (2003)Hum. Mol. Genet., 12, 497-508]. Increased levels of CREB have also been demonstrated to exert neuroprotective functions [Lonze & Ginty (2002)Neuron, 35, 605-623; Lonze et al. (2002)Neuron, 34, 371-385]. Our study aimed to investigate the distribution of CREB in the neuronal subpopulations of the striatum in normal rats compared to the HD model of quinolinic acid lesion. Twenty-five Wistar rats were administered quinolinic acid 100 mm into the right striatum, and killed after 24 h, 48 h, 1 week, 2 weeks, and six weeks, respectively. The contralateral striata were used as controls. Dual-label immunofluorescence was employed using antibodies against phosphorylated CREB and each of the different neuronal subpopulations markers. Our results show that activated CREB levels decrease progressively in projection neurons and parvalbumin (PARV) and calretinin (CALR) interneurons, whereas such levels remain stable in cholinergic and somatostatin interneurons. Thus, we speculate that the ability of cholinergic interneurons to maintain their levels of CREB after excitotoxic lesions is one of the factors determining their protection in Huntington's disease.

Animals↗
PubMed2005

Calcium-dependent dephosphorylation of brain mitochondrial calcium/cAMP response element binding protein (CREB).

Calcium-mediated signaling regulates nuclear gene transcription by calcium/cAMP response element binding protein (CREB) via calcium-dependent kinases and phosphatases. This study tested the hypothesis that CREB is also present in mitochondria and subject to dynamic calcium-dependent modulation of its phosphorylation state. Antibodies to CREB and phosphorylated CREB (pCREB) were used to demonstrate the presence of both forms in isolated mitochondria and mitoplasts from rat brain. When energized mitochondria were exposed to increasing concentrations of Ca2+ in the physiological range, pCREB was lost while total CREB remained constant. In the presence of Ru360, an inhibitor of the mitochondrial Ca2+ uptake uniporter, calcium-dependent loss of pCREB levels was attenuated, suggesting that intramitochondrial calcium plays an important role in pCREB dephosphorylation. pCREB dephosphorylation was not, however, inhibited by the phosphatase inhibitors okadaic acid and Tacrolimus. In the absence of Ca2+, CREB phosphorylation was elevated by the addition of ATP to the mitochondrial suspension. Exposure of mitochondria to the pore-forming molecule alamethicin that causes osmotic swelling and release of intermembrane proteins enriched mitochondrial pCREB immunoreactivity. These results further suggest that mitochondrial CREB is located in the matrix or inner membrane and that a kinase and a calcium-dependent phosphatase regulate its phosphorylation state.

Adenosine Triphosphate↗
PubMed2002

Inducible and brain region-specific CREB transgenic mice.

To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different lines of bitransgenic mice, and CREB expression was blocked by addition of doxycycline, an analog of tetracycline. Overexpression of CREB influenced the expression of other members of the CREB/ATF family of transcription factors, consistent with previous reports. In addition, psychostimulant induction of dynorphin, a neuropeptide regulated by drugs of abuse, was up-regulated in striatum. Finally, there was a significant reduction in cocaine-induced locomotor activity in the CREB bitransgenic mice. These results are consistent with a role for CREB in mediating adaptive changes that occur in response to drugs of abuse.

Animals↗
PubMed2000

Characterization of a CREB gain-of-function mutant with constitutive transcriptional activity in vivo.

The cyclic AMP (cAMP)-responsive factor CREB promotes cellular gene expression, following its phosphorylation at Ser133, via recruitment of the coactivator paralogs CREB-binding protein (CBP) and p300. CBP and p300, in turn, appear to mediate target gene induction via their association with RNA polymerase II complexes and via intrinsic histone acetyltransferase activities that mobilize promoter-bound nucleosomes. In addition to cAMP, a wide variety of stimuli, including hypoxia, UV irradiation, and growth factor addition, induce Ser133 phosphorylation with stoichiometry and kinetics comparable to those induced by cAMP. Yet a number of these signals are incapable of promoting target gene activation via CREB phosphorylation per se, suggesting the presence of additional regulatory events either at the level of CREB-CBP complex formation or in the subsequent recruitment of the transcriptional apparatus. Here we characterize a Tyr134Phe CREB mutant that behaves as a constitutive activator in vivo. Like protein kinase A (PKA)-stimulated wild-type CREB, the Tyr134Phe polypeptide was found to stimulate target gene expression via the Ser133-dependent recruitment of CBP and p300. Biochemical studies reveal that mutation of Tyr134 to Phe lowers the K(m) for PKA phosphorylation and thereby induces high levels of constitutive Ser133 phosphorylation in vivo. Consistent with its constitutive activity, Tyr134Phe CREB strongly promoted differentiation of PC12 cells in concert with suboptimal doses of nerve growth factor. Taken together, these results demonstrate that Ser133 phosphorylation is sufficient for cellular gene activation and that additional signal-dependent modifications of CBP or p300 are not required for recruitment of the transcriptional apparatus to the promoter.

Animals↗
PubMed2001

CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the interleukin-3 survival signal.

The Ces-2/E2A-HLF binding element (CBE) is recognized by Caenorhabditis elegans death specification gene product Ces-2 and human acute lymphocytic leukemia oncoprotein E2A-HLF. In an attempt to identify a cellular CBE-binding protein(s) that may be involved in apoptosis regulation in mammals, multiple nuclear binding complexes of CBE were identified in various mammalian cell lines and tissues by electrophoretic mobility shift assay. Cyclic AMP (cAMP)-responsive element (CRE)-binding protein (CREB) was present in one major CBE complex of Ba/F3 and TF-1 cells, and both in vitro-translated and Escherichia coli-synthesized CREB bound to CBE. Activation of CREB by cAMP-elevating chemicals or the catalytic subunit of protein kinase A (PKAc) resulted in induction of the CBE-driven reporter gene. Stimulation of Ba/F3 cells with interleukin-3 (IL-3) promptly induced phosphorylation of CREB at serine(133) partially via a PKA-dependent pathway. Consistently, Ba/F3 cell survival in the absence of IL-3 was prolonged by activation of PKA. Conversely, treatment of cells with a PKA inhibitor or expression of the dominant negative forms of the regulatory subunit type I of PKA and CREB overrode the survival activity of IL-3. Last, the bcl-2 gene was demonstrated to be one candidate cellular target of the CREB-containing CBE complex, as mutations in the CRE and CBE sites significantly reduced the IL-3 inducibility of the bcl-2 promoter. Together, our results suggest that CREB is one cellular counterpart of Ces-2/E2A-HLF and is part of IL-3 dependent apoptosis regulation in hematopoietic cells.

Animals↗
PubMed2002

Activating transcription factor 1 and CREB are important for cell survival during early mouse development.

Activating transcription factor 1 (ATF1), CREB, and the cyclic AMP (cAMP) response element modulatory protein (CREM), which constitute a subfamily of the basic leucine zipper transcription factors, activate gene expression by binding as homo- or heterodimers to the cAMP response element in regulatory regions of target genes. To investigate the function of ATF1 in vivo, we inactivated the corresponding gene by homologous recombination. In contrast to CREB-deficient mice, which suffer from perinatal lethality, mice lacking ATF1 do not exhibit any discernible phenotypic abnormalities. Since ATF1 and CREB but not CREM are strongly coexpressed during early mouse development, we generated mice deficient for both CREB and ATF1. ATF1(-/-) CREB(-/-) embryos die before implantation due to developmental arrest. ATF1(+/-) CREB(-/-) embryos display a phenotype of embryonic lethality around embryonic day 9.5 due to massive apoptosis. These results indicate that CREB and ATF1 act in concert to mediate signals essential for maintaining cell viability during early embryonic development.

Activating Transcription Factor 1↗