Mouse ATF-2 Null Mutants Display Features of a Severe Type of Meconium Aspiration Syndrome

Maekawa, Tomoko; Bernier, François; Sato, Motohiko; Nomura, Shosaku; Singh, Manjeet; Inoue, Yoshiro; Tokunaga, Tomoyuki; Imai, Hiroshi; Yokoyama, Minesuke; Reimold, Andreas M.; Glimcher, Laurie H.; Ishii, Shunsuke

doi:10.1074/jbc.274.25.17813

Cited by 101 publications

(84 citation statements)

References 28 publications

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“…There are no mutations identified in the dATF-2 locus, and the dATF-2 null mutant could be lethal, because the Atf-2 null mutant mice die immediately after birth because of a respiration defect (Maekawa et al, 1999). Therefore, we used the transgenic RNAi technique to analyze the function of dATF-2 in vivo (Kennerdell and Carthew, 2000).…”

Section: Generation Of Datf-2 Transgenic Fliesmentioning

confidence: 99%

“…Glyceroneogenesis is defined as the de novo synthesis of glycerol-3-phosphate from pyruvate, lactate, or certain amino acids. However, it is difficult to examine in a whole animal system whether ATF-2 is critical for metabolic regulation via regulating PEPCK expression, since Atf-2 null mutant mice die immediately after birth due to a respiration defect (Maekawa et al, 1999). Furthermore, no tissue-specific Atf-2 knockdown mice are available at present.…”

Section: Introductionmentioning

confidence: 99%

“…The target genes of c-Jun/ATF-2 heterodimers, which are implicated in growth control, include c-jun itself and interferon-␤ (van Dam et al, 1993;Falvo et al, 2000). The platelet-derived growth factor receptor ␣ gene, which is critical for proliferation of cytotrophoblasts, is an ATF-2 target and its expression level is decreased in the placenta of Atf-2 mutant mice (Maekawa et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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ATF-2 Regulates Fat Metabolism inDrosophila

Okamura

Shimizu²,

Nagao³

et al. 2007

MBoC

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ATF-2 is a member of the ATF/CREB family of transcription factors that is activated by stress-activated protein kinases such as p38. To analyze the physiological role of Drosophila ATF-2 (dATF-2), we generated dATF-2 knockdown flies using RNA interference. Reduced dATF-2 in the fat body, the fly equivalent of the mammalian liver and adipose tissue, decreased survival under starvation conditions. This was due to smaller triglyceride reserves of dATF-2 knockdown flies than control flies. Among multiple genes that control triglyceride levels, expression of the Drosophila PEPCK (dPEPCK) gene was strikingly reduced in dATF-2 knockdown flies. PEPCK is a key enzyme for both gluconeogenesis and glyceroneogenesis, which is a pathway required for triglyceride synthesis via glycerol-3-phosphate. Although the blood sugar level in dATF-2 knockdown flies was almost same as that in control flies, the activity of glyceroneogenesis was reduced in the fat bodies of dATF-2 knockdown flies. Thus, reduced glyceroneogenesis may at least partly contribute to decreased triglyceride stores in the dATF-2 knockdown flies. Furthermore we showed that dATF-2 positively regulated dPEPCK gene transcription via several CRE half-sites in the PEPCK promoter. Thus, dATF-2 is critical for regulation of fat metabolism.

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Section: Generation Of Datf-2 Transgenic Fliesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ATF-2 Regulates Fat Metabolism inDrosophila

Okamura

Shimizu²,

Nagao³

et al. 2007

MBoC

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“…Null Atf-2 mutant mice die shortly after birth and display symptoms of severe respiratory distress including lungs filled with meconium (Maekawa et al, 1999). By using Atf-2 À/À mouse embryonic fibroblasts (MEFs), we recently showed that ATF-2 plays a role in hypoxiainduced apoptosis (Maekawa et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

ATF-2 controls transcription of Maspin and GADD45α genes independently from p53 to suppress mammary tumors

Maekawa¹,

Sano²,

Shinagawa³

et al. 2007

Oncogene

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“…Mouse null mutants of ATF-2 died shortly after birth and displayed symptoms of severe respiratory distress with lungs filled with meconium (48). In the ATF-2-deficient mice, an increased level of TH mRNA was shown in the embryonic brain, and the authors attributed it to hypoxia in the mice (48).…”

Section: Discussionmentioning

confidence: 99%

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

Suzuki

Yamakuni

Hagiwara

et al. 2002

Journal of Biological Chemistry

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Transcriptional regulation of catecholamine-synthesizing genes is important for the determination of neurotransmitters during brain development. We found that three catecholamine-synthesizing genes were transcriptionally up-regulated in cloned PC12D cells overexpressing V-1, a protein that is highly expressed during postnatal brain development (1). To reveal the molecular mechanism to regulate the expression of tyrosine hydroxylase (TH), which is the rate-limiting enzyme for catecholamine biosynthesis, we analyzed the transcription factors responsible for TH induction in the V-1 clonal cells. First, by using reporter constructs, we found that the transcription mediated by cAMP-responsive element (CRE) was selectively enhanced in the V-1 cells, and TH promoter activity was totally dependent on the CRE in the promoter region of the TH gene. Next, immunoblot analyses and a transactivation assay using a GAL4 reporter system revealed that ATF-2, but not cAMP-responsive element-binding protein (CREB), was highly phosphorylated and activated in the V-1 cells, while both CREB and ATF-2 were bound to the TH-CRE. Finally, the enhanced TH promoter activity was competitively attenuated by expression of a plasmid containing the ATF-2 transactivation domain. These data demonstrated that activation of ATF-2 resulted in the increased transcription of the TH gene and suggest that ATF-2 may be deeply involved in the transcriptional regulation of catecholamine-synthesizing genes during neural development.Catecholamines are synthesized from L-tyrosine by the sequential action of four enzymes: tyrosine is converted to DOPA by tyrosine hydroxylase (TH), 1 DOPA to dopamine by aromatic L-amino acid decarboxylase (AADC), dopamine to norepinephrine by dopamine ␤-hydroxylase (DBH), and norepinephrine to epinephrine by phenylethanolamine N-methyltransferase. The regulation of the gene expression of these enzymes is important for the determination of the expression of neurotransmitters during brain development as well as for brain function under physiological and pathological conditions. TH is the rate-limiting enzyme for catecholamine biosynthesis. The transcriptional regulation of the TH gene has been extensively studied, and many transcription factors were suggested to regulate TH gene expression. CREB, ATF-1, and CREM were shown to recognize the cAMP-responsive element (CRE) located at position Ϫ45/Ϫ38 in the TH promoter (2-6). CREB was reported to mediate basal and cAMP-induced TH transcription in various cultured cells including PC12 cells by the use of dominant-negative CREB protein and antisense RNA against CREB (7-10). CREB is activated by phosphorylation on Ser 133 (11,12). The activation of CREB by phosphorylation has been shown to mediate PKA-dependent (7, 13-15) and -independent (13, 14) induction of TH transcription. Functional and physiological roles of ATF-1 and CREM for TH transcription remained unclear. AP-1 transcription factors bound to the TPA-responsive element located at Ϫ205/Ϫ199 in the TH promoter, which also plays ...

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Mouse ATF-2 Null Mutants Display Features of a Severe Type of Meconium Aspiration Syndrome

Cited by 101 publications

References 28 publications

ATF-2 Regulates Fat Metabolism inDrosophila

ATF-2 Regulates Fat Metabolism inDrosophila

ATF-2 controls transcription of Maspin and GADD45α genes independently from p53 to suppress mammary tumors

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

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