Acheron, an novel LA antigen family member, binds to cask and forms a complex with id transcription factors

AbstractAcheron, a Lupus antigen ortholog, was identified as a novel death-associated transcript from the intersegmental muscles of the mothManduca sexta. Acheron is phylogenetically-conserved and represents a new sub-family of Lupus antigen proteins. Acheron is expressed predominantly in neurons and muscle in vertebrates, and regulates several developmental events including myogenesis, neurogenesis and possibly metastasis. Using Acheron as bait, we performed a yeast two-hybrid screen with a mouse embryo cDNA library and identified CASK-C, a novel CASK/Lin-2 isoform, as an Acheron binding partner. Acheron and CASK-C bind via the C-terminus of Acheron and the CaMKII-like domain of CASK-C. Co-immunoprecipitation assays verify this interaction and demonstrate that Acheron also forms a complex with all members of the Id (inhibitor of differentiation) proteins. Taken together, these data suggest a mechanism by which Acheron may regulate development and pathology.

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Inhibition of forkhead box class O family member transcription factors in rheumatoid synovial tissue

Arthritis & Rheumatism ◽

10.1002/art.22653 ◽

2007 ◽

Vol 56 (7) ◽

pp. 2180-2191 ◽

Cited By ~ 31

Author(s):

J. Ludikhuize ◽

D. de Launay ◽

D. Groot ◽

T. J. M. Smeets ◽

M. Vinkenoog ◽

...

Keyword(s):

Transcription Factors ◽

Family Member ◽

Synovial Tissue ◽

Forkhead Box ◽

Rheumatoid Synovial Tissue

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Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues

Cells ◽

10.3390/cells8111373 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1373 ◽

Cited By ~ 11

Author(s):

Herring ◽

Elison ◽

Tessem

Keyword(s):

Transcription Factors ◽

Family Member ◽

Nuclear Receptors ◽

Hormone Receptors ◽

Cellular Proliferation ◽

Nuclear Hormone Receptors ◽

Fuel Utilization ◽

Orphan Nuclear Receptors ◽

Tissue Specific ◽

Specific Effects

The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest, the Nr4a family impinge, in a tissue dependent fashion, on cellular proliferation, apoptosis and fuel utilization. The regulation of these processes occurs through both nuclear and non-genomic pathways. The purpose of this review is to provide a balanced perspective of the tissue specific and Nr4a family member specific, effects on cellular proliferation, apoptosis and fuel utilization.

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Conserved and divergent roles for members of the Snail family of transcription factors in the chick and mouse embryo

Development ◽

10.1242/dev.125.16.3111 ◽

1998 ◽

Vol 125 (16) ◽

pp. 3111-3121 ◽

Cited By ~ 16

Author(s):

M. Sefton ◽

S. Sanchez ◽

M.A. Nieto

Keyword(s):

Transcription Factors ◽

Amino Acid ◽

Chick Embryo ◽

Neural Crest ◽

Family Member ◽

Zinc Finger ◽

Mouse Embryo ◽

Amino Acid Sequences ◽

Mouse Homologue ◽

Snail Family

The members of the Snail family of zinc-finger transcription factors have been implicated in the formation of distinct tissues within the developing vertebrate and invertebrate embryo. Two members of this family have been described in higher vertebrates, Snail (Sna) and Slug (Slu), where they have been implicated in the formation of tissues such as the mesoderm and the neural crest. We have isolated the mouse homologue of the Slu gene enabling us to analyse and compare the amino acid sequences and the patterns of expression of both Sna and Slu in the chick and mouse. We have detected features in the sequences that allow the unequivocal ascription of any family member to the Sna or Slu subfamilies and we have observed that, during early stages of development, many of the sites of Slu and Sna expression in the mouse and chick embryo are swapped. Later in development, the sites of expression of Slu and Sna are conserved between these two species. These data, together with the data available in other species, lead us to propose that Slu and Sna arose as a duplication of an ancestor gene and that an extra duplication in the fish lineage has given rise to two Sna genes. Furthermore, several early sites of Slu and Sna expression have been swapped in the avian lineage. Our analysis of the Snail family may also shed new light on the origin of the neural crest.

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Unraveling the transcriptional determinants of liver sinusoidal endothelial cell specialization

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00215.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. G803-G815

Author(s):

Willeke de Haan ◽

Cristina Øie ◽

Mohammed Benkheil ◽

Wouter Dheedene ◽

Stefan Vinckier ◽

...

Keyword(s):

Endothelial Cells ◽

Transcription Factors ◽

Family Member ◽

Binding Protein ◽

Organic Anion ◽

Transcriptional Regulators ◽

Liver Cells ◽

Liver Sinusoidal Endothelial Cell ◽

Liver Sinusoidal Endothelial Cells ◽

Sinusoidal Endothelial Cells

Liver sinusoidal endothelial cells (LSECs) are the first liver cells to encounter waste macromolecules, pathogens, and toxins in blood. LSECs are highly specialized to mediate the clearance of these substances via endocytic scavenger receptors and are equipped with fenestrae that mediate the passage of macromolecules toward hepatocytes. Although some transcription factors (TFs) are known to play a role in LSEC specialization, information about the specialized LSEC signature and its transcriptional determinants remains incomplete. Based on a comparison of liver, heart, and brain endothelial cells (ECs), we established a 30-gene LSEC signature comprising both established and newly identified markers, including 7 genes encoding TFs. To evaluate the LSEC TF regulatory network, we artificially increased the expression of the 7 LSEC-specific TFs in human umbilical vein ECs. Although Zinc finger E-box-binding protein 2, homeobox B5, Cut-like homolog 2, and transcription factor EC (TCFEC) had limited contributions, musculoaponeurotic fibrosarcoma (C-MAF), GATA binding protein 4 (GATA4), and MEIS homeobox 2 (MEIS2) emerged as stronger inducers of LSEC marker expression. Furthermore, a combination of C-MAF, GATA4, and MEIS2 showed a synergistic effect on the increase of LSEC signature genes, including liver/lymph node-specific ICAM-3 grabbing non-integrin ( L-SIGN) (or C-type lectin domain family member M ( CLEC4M)), mannose receptor C-Type 1 ( MRC1), legumain ( LGMN), G protein-coupled receptor 182 ( GPR182), Plexin C1 ( PLXNC1), and solute carrier organic anion transporter family member 2A1 ( SLCO2A1). Accordingly, L-SIGN, MRC1, pro-LGMN, GPR182, PLXNC1, and SLCO2A1 protein levels were elevated by this combined overexpression. Although receptor-mediated endocytosis was not significantly induced by the triple TF combination, it enhanced binding to E2, the hepatitis C virus host-binding protein. We conclude that C-MAF, GATA4, and MEIS2 are important transcriptional regulators of the unique LSEC fingerprint and LSEC interaction with viruses. Additional factors are however required to fully recapitulate the molecular, morphological, and functional LSEC fingerprint. NEW & NOTEWORTHY Liver sinusoidal endothelial cells (LSECs) are the first liver cells to encounter waste macromolecules, pathogens, and toxins in the blood and are highly specialized. Although some transcription factors are known to play a role in LSEC specialization, information about the specialized LSEC signature and its transcriptional determinants remains incomplete. Here, we show that Musculoaponeurotic Fibrosarcoma (C-MAF), GATA binding protein 4 (GATA4), and Meis homeobox 2 (MEIS2) are important transcriptional regulators of the unique LSEC signature and that they affect the interaction of LSECs with viruses.

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335 BCL-2 FAMILY MEMBER MCL-1 INTERACTS WITH THE P53 FAMILY OF TRANSCRIPTION FACTORS

Journal of Hepatology ◽

10.1016/s0168-8278(12)60348-1 ◽

2012 ◽

Vol 56 ◽

pp. S136-S137

Author(s):

M. Meinhard ◽

L. Koenig ◽

A. Pelc ◽

A. Lovas ◽

N. Joschko ◽

...

Keyword(s):

Transcription Factors ◽

Family Member ◽

P53 Family

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Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway?

Oncogene ◽

10.1038/sj.onc.1203634 ◽

2000 ◽

Vol 19 (29) ◽

pp. 3266-3277 ◽

Cited By ~ 52

Author(s):

Germana Meroni ◽

Stefano Cairo ◽

Giuseppe Merla ◽

Silvia Messali ◽

Roger Brent ◽

...

Keyword(s):

Transcription Factors ◽

Family Member ◽

Regulatory Pathway ◽

Center Stage

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Loss of PU.1 expression is associated with defective immunoglobulin transcription in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease

Blood ◽

10.1182/blood.v99.8.3060 ◽

2002 ◽

Vol 99 (8) ◽

pp. 3060-3062 ◽

Cited By ~ 62

Author(s):

Franziska Jundt ◽

Katharina Kley ◽

Ioannis Anagnostopoulos ◽

Kristina Schulze Pröbsting ◽

Axel Greiner ◽

...

Keyword(s):

Transcription Factors ◽

B Cell ◽

Family Member ◽

Hodgkin Disease ◽

Immunoglobulin Genes ◽

Down Regulation ◽

Enhancer Activity ◽

Ets Family

Abstract Immunoglobulin transcription is impaired in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD). We recently demonstrated that defective immunoglobulin promoter transcription correlates with the down-regulation of the B-cell transcription factors Oct2 and BOB.1/OBF.1. These results prompted us to investigate whether immunoglobulin enhancer activity is also impaired in HRS cells and whether as yet unidentified factors could be necessary for immunoglobulin enhancer activity in HRS cells of cHD. Here we analyzed 30 cases of cHD for expression of the Ets family member PU.1 that is known to collaborate with multiple transcription factors and to regulate expression of immunoglobulin genes. We show that PU.1 is not expressed in primary and cultured HRS cells. Reintroduction of PU.1 and Oct2 in cultured HRS cells restored the activity of cotransduced immunoglobulin enhancer constructs. Our study identifies PU.1 deficiency as a recurrent defect in HRS cells that might contribute to their impairment of immunoglobulin transcription.

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Regulation of caspase-3 and -9 activation in oxidant stress to RTE by forkhead transcription factors, Bcl-2 proteins, and MAP kinases

AJP Renal Physiology ◽

10.1152/ajprenal.00391.2003 ◽

2004 ◽

Vol 287 (6) ◽

pp. F1258-F1268 ◽

Cited By ~ 38

Author(s):

Gur P. Kaushal ◽

Ling Liu ◽

Varsha Kaushal ◽

Xiaoman Hong ◽

Oksana Melnyk ◽

...

Keyword(s):

Cell Death ◽

Transcription Factors ◽

Family Member ◽

Caspase 3 ◽

Oxidant Stress ◽

Caspase Activation ◽

Oxidant Injury ◽

Kinase Inhibition ◽

Forkhead Transcription Factors ◽

The Impact

Cytotoxicity to renal tubular epithelial cells (RTE) is dependent on the relative response of cell survival and cell death signals triggered by the injury. Forkhead transcription factors, Bcl-2 family member Bad, and mitogen-activated protein kinases are regulated by phosphorylation that plays crucial roles in determining cell fate. We examined the role of phosphorylation of these proteins in regulation of H2O2-induced caspase activation in RTE. The phosphorylation of FKHR, FKHRL, and Bcl-2 family member Bad was markedly increased in response to oxidant injury, and this increase was associated with elevated levels of basal phosphorylation of Akt/protein kinase B. Phosphoinositol (PI) 3-kinase inhibitors abolished this phosphorylation and also decreased expression of antiapoptotic proteins Bcl-2 and BclxL. Inhibition of phosphorylation of forkhead proteins resulted in a marked increase in the proapoptotic protein Bim. These downstream effects of PI 3-kinase inhibition promoted the oxidant-induced activation of caspase-3 and -9, but not caspase-8 and -1. The impact of enhanced activation of caspases by PI 3-kinase inhibition was reflected on accelerated oxidant-induced cell death. Oxidant stress also induced marked phosphorylation of ERK1/2, P38, and JNK kinases. Inhibition of ERK1/2 phosphorylation but not P38 and JNK kinase increased caspase-3 and -9 activation; however, this activation was far less than induced by inhibition of Akt phosphorylation. Thus the Akt-mediated phosphorylation pathway, ERK signaling, and the antiapoptotic Bcl-2 proteins distinctly regulate caspase activation during oxidant injury to RTE. These studies suggest that enhancing renal-specific survival signals may lead to preservation of renal function during oxidant injury.

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A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3) cooperates with XFast-1 in regulating gastrulation movements

Development ◽

10.1242/dev.129.12.2823 ◽

2002 ◽

Vol 129 (12) ◽

pp. 2823-2834 ◽

Cited By ~ 1

Author(s):

Michael Howell ◽

Gareth J. Inman ◽

Caroline S. Hill

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Family Member ◽

Antisense Oligonucleotides ◽

Family Members ◽

Convergent Extension ◽

Forkhead Transcription Factor ◽

Xenopus Embryos

In early Xenopus embryos, the prototypical XFast-1/Smad2/Smad4 complex ARF1 is induced at the Mix.2 ARE by activin overexpression. We have characterised ARF2, a related, but much more abundant, complex formed during gastrulation in response to endogenous TGFβ family members and we have identified a novel Fast family member, XFast-3, as its transcription factor component. Endogenous ARF2 efficiently competes out ARF1 at early gastrulation, due to the ability of XFast-3 to interact with activated Smads with much higher affinity than XFast-1. We demonstrate that ARF1 and ARF2 are activated by distinct TGFβ family members. Using morpholino antisense oligonucleotides to deplete levels of the constituent transcription factors XFast-1 and XFast-3 specifically, we demonstrate an important role for ARF1 and ARF2 in early Xenopus embryos in controlling the convergent extension movements of gastrulation.

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