Structural Basis for DNA Recognition by the Basic Region Leucine Zipper Transcription Factor CCAAT/Enhancer-binding Protein α

Miller, Maria; Shuman, Jon D.; Sebastian, Thomas; Dauter, Zbigniew; Johnson, Peter F.

doi:10.1074/jbc.m300417200

Cited by 127 publications

(127 citation statements)

References 40 publications

(39 reference statements)

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“…6B). In contrast, the C/EBP␤ mutants, Y274F and L320R, which affect DNA binding and protein dimerization, respectively (55,61), decreased the GADD45␤-dependent activities of both Col10a1 and C/EBP reporters (Fig. 6, A and B).…”

Section: C/ebp␤ Threonine 235 Mutation Disrupts Its Activation By Gadmentioning

confidence: 99%

GADD45β Enhances Col10a1 Transcription via the MTK1/MKK3/6/p38 Axis and Activation of C/EBPβ-TAD4 in Terminally Differentiating Chondrocytes

Tsuchimochi

Otero

Dragomir

et al. 2010

Journal of Biological Chemistry

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GADD45␤ (growth arrest-and DNA damage-inducible) interacts with upstream regulators of the JNK and p38 stress response kinases. Previously, we reported that the hypertrophic zone of the Gadd45␤ ؊/؊ mouse embryonic growth plate is compressed, and expression of type X collagen (Col10a1) and matrix metalloproteinase 13 (Mmp13) genes is decreased. Herein, we report that GADD45␤ enhances activity of the proximal Col10a1 promoter, which contains evolutionarily conserved AP-1, cAMP-response element, and C/EBP half-sites, in synergism with C/EBP family members, whereas the MMP13 promoter responds to GADD45␤ together with AP-1, ATF, or C/EBP family members. C/EBP␤ expression also predominantly co-localizes with GADD45␤ in the embryonic growth plate. Moreover, GADD45␤ enhances C/EBP␤ activation via MTK1, MKK3, and MKK6, and dominant-negative p38␣apf, but not JNKapf, disrupts the combined trans-activating effect of GADD45␤ and C/EBP␤ on the Col10a1 promoter. Importantly, GADD45␤ knockdown prevents p38 phosphorylation while decreasing Col10a1 mRNA levels but does not affect C/EBP␤ binding to the Col10a1 promoter in vivo, indicating that GADD45␤ influences the transactivation function of DNA-bound C/EBP␤. In support of this conclusion, we show that the evolutionarily conserved TAD4 domain of C/EBP␤ is the target of the GADD45␤-dependent signaling. Collectively, we have uncovered a novel molecular mechanism linking GADD45␤ via the MTK1/MKK3/6/p38 axis to C/EBP␤-TAD4 activation of Col10a1 transcription in terminally differentiating chondrocytes.

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Section: C/ebp␤ Threonine 235 Mutation Disrupts Its Activation By Gadmentioning

confidence: 99%

GADD45β Enhances Col10a1 Transcription via the MTK1/MKK3/6/p38 Axis and Activation of C/EBPβ-TAD4 in Terminally Differentiating Chondrocytes

Tsuchimochi

Otero

Dragomir

et al. 2010

Journal of Biological Chemistry

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“…In all, 35 cycles of c-Jun and G6PD amplification conditions were: 951C for 10 min; 951C for 0.5 s; 641C for 10 s; 721C for 25 s. Running the samples on 1.2% agarose gel, the PCR fragment size of 400 bps for c-Jun and 340 bps for G6PD were observed. (Miller et al, 2003). In conclusion, c-Jun binds to C/EBPa via the leucine zipper domains and prevents C/EBPa DNA binding.…”

Section: Elevated C-jun Expression In Amlmentioning

confidence: 99%

Elevated c-Jun expression in acute myeloid leukemias inhibits C/EBPα DNA binding via leucine zipper domain interaction

Rangatia¹,

Vangala²,

Singh³

et al. 2003

Oncogene

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“…1A, left panel). As documented (25,26), the C/EBP␣ prefers to bind to the consensus sequence GCAAT in the promoters of its target genes. Bioinformatic analysis showed that there was such a potential C/EBP␣ binding site between Ϫ48 to Ϫ42 bp of the galectin-1 gene (Fig.…”

Section: C/ebp␣ Transcriptionally Up-regulates the Expression Of Galementioning

confidence: 99%

Synergistic Induction of Galectin-1 by CCAAT/Enhancer Binding Protein α and Hypoxia-inducible Factor 1α and Its Role in Differentiation of Acute Myeloid Leukemic Cells

Zhao

Jiang

et al. 2011

Journal of Biological Chemistry

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Background: Galectin-1 is a widely investigated cell surface glycoprotein-binding protein that mediates multiple cellular activities. Results: Galectin-1 is synergistically induced by C/EBP␣ and HIF-1␣ and facilitates the differentiation of leukemic cells. Conclusion: Galectin-1 is an important mediator for leukemic cell differentiation. Significance: Learning how galectin-1 expression is regulated by hematopoietic cell differentiation-associated transcriptional factors is of significance in understanding leukemic cell differentiation.

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Structural Basis for DNA Recognition by the Basic Region Leucine Zipper Transcription Factor CCAAT/Enhancer-binding Protein α

Cited by 127 publications

References 40 publications

GADD45β Enhances Col10a1 Transcription via the MTK1/MKK3/6/p38 Axis and Activation of C/EBPβ-TAD4 in Terminally Differentiating Chondrocytes

GADD45β Enhances Col10a1 Transcription via the MTK1/MKK3/6/p38 Axis and Activation of C/EBPβ-TAD4 in Terminally Differentiating Chondrocytes

Elevated c-Jun expression in acute myeloid leukemias inhibits C/EBPα DNA binding via leucine zipper domain interaction

Synergistic Induction of Galectin-1 by CCAAT/Enhancer Binding Protein α and Hypoxia-inducible Factor 1α and Its Role in Differentiation of Acute Myeloid Leukemic Cells

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