Coordination of NF-κB and NFAT Antagonism by the Forkhead Transcription Factor Foxd1

Li, Gang; Peng, Stanford L.

doi:10.4049/jimmunol.176.8.4793

Cited by 31 publications

(24 citation statements)

References 35 publications

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“…For example, FOXD1 and FOXD3 TFBSs were identified in genes upregulated by the HPIV1 C mutant viruses. Only recently has an important role for FoxD1 in the regulation of immune activation through the NF-B pathway been identified (42). FoxD3 is well known for controlling cellular differentiation, but no role for FoxD3 in the regulation of the immune response or the response to viral infection has yet been defined.…”

Section: F170smentioning

confidence: 99%

The C Proteins of Human Parainfluenza Virus Type 1 (HPIV1) Control the Transcription of a Broad Array of Cellular Genes That Would Otherwise Respond to HPIV1 Infection

Boonyaratanakornkit

Bartlett

Amaro-Carambot

et al. 2009

J Virol

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Human parainfluenza virus type 1 (HPIV1) is an important respiratory pathogen in children and the most common cause of viral croup. We performed a microarray-based analysis of gene expression kinetics to examine how wild-type (wt) HPIV1 infection altered gene expression in human respiratory epithelial cells and what role beta interferon played in this response. We similarly evaluated HPIV1-P(C؊), a highly attenuated and apoptosis-inducing virus that does not express any of the four C proteins, and HPIV1-C F170S , a less attenuated mutant that contains a single point mutation in C and, like wt HPIV1, does not efficiently induce apoptosis, to examine the role of the C proteins in controlling host gene expression. We also used these data to investigate whether the phenotypic differences between the two C mutants could be explained at the transcriptional level. Mutation or deletion of the C proteins of HPIV1 permitted the activation of over 2,000 cellular genes that otherwise would be repressed by HPIV1 infection. Thus, the C proteins profoundly suppress the response of human respiratory cells to HPIV1 infection. Cellular pathways targeted by the HPIV1 C proteins were identified and their transcriptional control was analyzed using bioinformatics. Transcription factor binding sites for IRF and NF-B were overrepresented in some of the C protein-targeted pathways, but other pathways were dominated by less-known factors, such as forkhead transcription factor FOXD1. Surprisingly, the host responses to the P(C؊) and C F170S mutants were very similar, and only subtle differences in the expression kinetics of caspase 3 and TRAIL receptor 2 were observed. Thus, changes in host cell transcription did not reflect the striking phenotypic differences observed between these two viruses.

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Section: F170smentioning

confidence: 99%

The C Proteins of Human Parainfluenza Virus Type 1 (HPIV1) Control the Transcription of a Broad Array of Cellular Genes That Would Otherwise Respond to HPIV1 Infection

Boonyaratanakornkit

Bartlett

Amaro-Carambot

et al. 2009

J Virol

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“…Studies in model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus have demonstrated a pivotal role for Fox family transcription factors in embryonic patterning, development, and metabolism (1). Recent elucidation of roles for this family of transcriptional regulators in thymic development (Foxn1), lineage commitment (Foxp3), and function of lymphocytes (Foxj1, Foxo3, and Foxd1) has firmly established a role for this transcription factor family in the development and maintenance of normal immune responses (2,3).…”

Section: T He Forkhead (Fkh)mentioning

confidence: 99%

Analysis of FOXP3 Reveals Multiple Domains Required for Its Function as a Transcriptional Repressor

Lopes

Torgerson

Schubert

et al. 2006

The Journal of Immunology

245

254

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Foxp3 has been shown to be both necessary and sufficient for the development and function of naturally arising CD4+CD25+ regulatory T cells in mice. Mutation of Foxp3 in Scurfy mice and FOXP3 in humans with IPEX results in fatal, early onset autoimmune disease and demonstrates the critical role of FOXP3 in maintaining immune homeostasis. The FOXP3 protein encodes several functional domains, including a C2H2 zinc finger, a leucine zipper, and a winged-helix/forkhead (FKH) domain. We have shown previously that FOXP3 functions as a transcriptional repressor and inhibits activation-induced IL-2 gene transcription. To characterize the role of each predicted functional domain on the in vivo activity of FOXP3, we have evaluated the location of point mutations identified in a large cohort of patients with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) and found them to cluster primarily within the FKH domain and the leucine zipper, but also present within the poorly defined N-terminal portion of the protein. The molecular functions of each of the IPEX-targeted domains were investigated. We show that FOXP3 is constitutively localized to the nucleus and this localization requires sequences at both the amino and C-terminal ends of its FKH domain. Moreover, FOXP3 was found to homodimerize through its leucine zipper. We also identify a novel functional domain within the N-terminal half of FOXP3, which is required for FOXP3-mediated repression of transcription from both a constitutively active and a NF-AT-inducible promoter. Furthermore, we demonstrate that IPEX mutations in these domains correlate with deficiencies in FOXP3 repressor function, corroborating their in vivo relevance.

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“…Mariani & Harland (1998) showed that Xbf2 is a transcriptional repressor that could convert ectoderm into neural tissue. In addition, Foxd1 can mod- ulate inflammatory reactions and prevents autoimmunity by directly regulating anti-inflammatory regulators of the NF-AT (nuclear factor of activated T cells) pathway and by coordinating the suppression of the NF-κB (nuclear factor kappa B) pathway via Foxj1 (Lin & Peng 2006). At present, much attention was paid to the function of FoxD1 in kidney and neural development in higher vertebrates, but its function in muscle development, derivative of mesoderm, especially in fish species, is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Flounder (Paralichthys olivaceus) FoxD1 and its regulation on the expression of myogenic regulatory factor, MyoD

et al. 2012

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It has been reported that FoxD1 plays important roles in formation of several different tissues, such as retina and kidney in vertebrates. The function of FoxD1 in muscle development is, however, unclear although it is expressed in muscle cells in zebrafish. Muscles are the major tissue in fish, which serves as a rich protein source in our diet. To further understand the function of FoxD1 in fish muscle development, here we isolated and characterized the FoxD1 gene from flounder (Paralichthys olivaceus), a valuable sea food and an important fish species in aquaculture in Asia. We analyzed its expression pattern and function in regulating myogenic regulatory factor, MyoD, one of the earliest marker of myogenic commitment. In situ hybridization revealed that FoxD1 was expressed in the tailbud, adaxial cells, posterior intestine, forebrain, midbrain and half of the retina in flounder embryos. Functional studies demonstrated that when flounder FoxD1 was over-expressed in zebrafish by microinjection, MyoD expression was decreased, suggesting that FoxD1 may be involved in myogenesis by regulating the expression of MyoD.

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Coordination of NF-κB and NFAT Antagonism by the Forkhead Transcription Factor Foxd1

Cited by 31 publications

References 35 publications

The C Proteins of Human Parainfluenza Virus Type 1 (HPIV1) Control the Transcription of a Broad Array of Cellular Genes That Would Otherwise Respond to HPIV1 Infection

The C Proteins of Human Parainfluenza Virus Type 1 (HPIV1) Control the Transcription of a Broad Array of Cellular Genes That Would Otherwise Respond to HPIV1 Infection

Analysis of FOXP3 Reveals Multiple Domains Required for Its Function as a Transcriptional Repressor

Flounder (Paralichthys olivaceus) FoxD1 and its regulation on the expression of myogenic regulatory factor, MyoD

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