Schnurri interacts with Mad in a Dpp‐dependent manner

Udagawa, Yoshiyuki; Hanai, Jun‐ichi; Tada, Keiichiro; Grieder, Nicole C.; Momoeda, Mikio; Taketani, Yuji; Affolter, Markus; Kawabata, Masahiro; Miyazono, Kohei

doi:10.1046/j.1365-2443.2000.00328.x

Cited by 31 publications

(31 citation statements)

References 65 publications

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“…3A). However, we, and others, have shown that Drosophila Shn contains at least two additional Smad-interacting domains (Dai et al, 2000;Udagawa et al, 2000), raising the possibility that interactions through other regions contribute to hShn1-Smad complex formation on the Xvent2-BRE. We therefore sought to identify and localize potential Smad-interacting regions within hShn1 by co-expressing hShn1 fragments with hSmad1 and an activated Bmp receptor.…”

Section: Vertebrate Shn Interacts Directly With Smad Proteins and Assmentioning

confidence: 76%

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Schnurri transcription factors fromDrosophilaand vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism

et al. 2006

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Bone Morphogenetic Proteins (Bmps) are secreted growth factors that play crucial roles in animal development across the phylogenetic spectrum. Bmp signaling results in the phosphorylation and nuclear translocation of Smads, downstream signal transducers that bind DNA. In Drosophila, the zinc finger protein Schnurri (Shn) plays a key role in signaling by the Bmp2/Bmp4 homolog Decapentaplegic (Dpp), by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene. Brk is a transcriptional repressor that downregulates Dpp target genes. Thus, brk inhibition by Shn results in the upregulation of Dpp-responsive genes. We present evidence that vertebrate Shn homologs can also mediate Bmp responsiveness through a mechanism similar to Drosophila Shn. We find that a Bmp response element (BRE) from the Xenopus Vent2 promoter drives Dppdependent expression in Drosophila. However, in sharp contrast to its activating role in vertebrates, the frog BRE mediates repression in Drosophila. Remarkably, despite these opposite transcriptional polarities, sequence changes that abolish cis-element activity in Drosophila also affect BRE function in Xenopus. These similar cis requirements reflect conservation of trans-acting factors, as human Shn1 (hShn1; HIVEP1) can interact with Smad1/Smad4 and assemble an hShn1/Smad complex on the BRE. Furthermore, both Shn and hShn1 activate the BRE in Xenopus embryos, and both repress brk and rescue embryonic patterning defects in shn mutants. Our results suggest that vertebrate Shn proteins function in Bmp signal transduction, and that Shn proteins recruit coactivators and co-repressors in a context-dependent manner, rather than acting as dedicated activators or repressors.

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Section: Vertebrate Shn Interacts Directly With Smad Proteins and Assmentioning

confidence: 76%

“…Drosophila Schnurri (Shn) is a large DNA-binding transcription factor with multiple, widely separated zinc finger domains, and was one of the first partners identified for Bmp-specific R-Smads (Dai et al, 2000;Udagawa et al, 2000). Shn localizes to the nucleus and interacts with Mad and Med in response to Dpp signaling.…”

Section: Introductionmentioning

confidence: 99%

Schnurri transcription factors fromDrosophilaand vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism

et al. 2006

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“…A critical transcription factor mediating this DPP-dependent repression of brinker is the zinc finger DNA-binding protein Schnurri (Shn; German for whiskers; Arora et al, 1995;Grieder et al, 1995;Staehling-Hampton et al, 1995). shn encodes a large protein (ϳ275 kDa) composed of eight zinc fingers (arranged in four clusters), which interacts with Smads (Mad and Medea, orthologs of vertebrate Smads 1/5/8 and 4, respectively) to mediate DPP signaling (Dai et al, 2000;Udagawa et al, 2000). In response to DPP/BMP signaling (Fig.…”

Section: Schnurri a Transcriptional Partner With Multiple Personalitiesmentioning

confidence: 99%

Finding partners: How BMPs select their targets

Blitz

Cho

2009

Developmental Dynamics

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The bone morphogenetic protein (BMP) signaling pathway is a conserved and evolutionarily ancient regulatory module affecting a large variety of cellular behaviors. The evolutionary flexibility in using BMP responses presumably arose by co-option of a canonical BMP signaling cascade to regulate the transcription of diverse batteries of target genes. This begs the question of how seemingly interchangeable BMP signaling components elicit widely different outputs in different cell types, an important issue in the context of understanding how BMP signaling integrates with gene regulatory networks to control development. Because a molecular understanding of how BMP signaling activates different batteries of target genes is an essential prerequisite to comprehending the roles of BMPs in regulating cellular responses, here we review the current knowledge of how BMP-regulated target genes are selected by the signal transduction machinery. We highlight recent studies suggesting the evolutionary conservation of BMP target gene regulation signaling by Schnurri family zinc finger proteins.

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“…An additional stretch of 31 amino acids in XHIVEP1, located between the ZAS-N and isolated zinc fingers (amino acids 703-733), is also weakly conserved between HIVEP1/2 and Drosophila Schnurri proteins. A larger protein fragment of Schnurri that contains this sequence element was shown to form homo-oligomers in vitro [24]. Our data indicate that the HIVEP/Shn protein family has retained remarkable conservation in their overall structure as well as in the sequence of specific domains in different vertebrate species.…”

Section: Discussionmentioning

confidence: 74%

“…The finding that HIVEP members directly interact with members of the Smad family, led us to investigate TGF-b responsive elements for Shn binding sites [21,23,24]. One well characterized TGF-b responsive promoter is that of Xvent-2B [36,37].…”

Section: Dna Binding Specificity Of Xenopus Hivepmentioning

confidence: 99%

Isolation and characterization of the Xenopus HIVEP gene family

Dürr¹,

Henningfeld²,

Hollemann³

et al. 2004

European Journal of Biochemistry

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The HIVEP gene family encodes for very large sequencespecific DNA binding proteins containing multiple zinc fingers. Three mammalian paralogous genes have been identified, HIVEP1, -2 and -3, as well as the closely related Drosophila gene, Schnurri. These genes have been found to directly participate in the transcriptional regulation of a variety of genes. Mammalian HIVEP members have been implicated in signaling by TNF-a and in the positive selection of thymocytes, while Schnurri has been shown to be an essential component of the TGF-b signaling pathway. In this study, we describe the isolation of Xenopus HIVEP1, as well as partial cDNAs of HIVEP2 and -3. Analysis of the temporal and spatial expression of the XHIVEP transcripts during early embryogenesis revealed ubiquitous expression of the transcripts. Assays using Xenopus oocytes mapped XHIVEP1 domains that are responsible for nuclear export and import activity. The DNA binding specificity of XHIVEP was characterized using a PCR-mediated selection and gel mobility shift assays.Keywords: DNA binding; Schnurri; Xenopus; zinc finger.The HIVEP family of zinc finger proteins regulates a diverse array of developmental and biological processes through direct DNA binding, as well as interaction with other transcription factors and components of signal transduction pathways [1,2]. Representative members include three human genes: [7,8] and HIVEP3 (ZAS3/Shn3) [7,9], as well as the corresponding mouse homologues aACRYBP1 [10,11], MIBP1 [12] and KRC [13]. Schnurri (Shn), a distantly related ortholog from Drosophila, which is most closely related to HIVEP1, has also been isolated and characterized [14][15][16].Typically, the large zinc finger (Znf) DNA binding proteins have a molecular mass greater than 250 kDa and contain two ZAS domains (N and C) that are widely separated in the primary sequence [2,9]. Each ZAS domain harbors a pair of DNA binding C 2 H 2 type zinc fingers followed by an acidic domain located in close proximity to a serine/threonine-rich sequence. The HIVEP family also has cellular regulatory activities not associated with DNA binding. KRC was shown to regulate the response of the TNF receptor to proinflammatory stimuli via the interaction with the adapter TRAF2 [1]. In addition, knockout studies in mouse have demonstrated that Shn2 plays a pivotal role in the positive selection of thymocytes [20,21]. However, the molecular mechanism for this observation remains undefined.Drosophila Shn is the most functionally characterized HIVEP member and has been shown to be essential for signaling by the TGF-b superfamily ligand, decapentaplegic (dpp), during anterior-posterior patterning of the wing [22]. Shn mutants mimic a large number of dpp loss-of-function phenotypes and mutations in the Dpp-receptors tkv and punt [15,16]. Cells that lack Shn do not respond to ectopic Dpp [14,15,23]. In response to Dpp, Shn was found to form a complex with Mad and Medea, the intracellular transducers of Dpp signaling [23,24]. Taken together, these results suggest that Shn act...

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Schnurri interacts with Mad in a Dpp‐dependent manner

Cited by 31 publications

References 65 publications

Schnurri transcription factors fromDrosophilaand vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism

Schnurri transcription factors fromDrosophilaand vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism

Finding partners: How BMPs select their targets

Isolation and characterization of the Xenopus HIVEP gene family

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