DDC‐4, an apoptosis‐associated gene, is a secreted frizzled relative

Wolf, Vladimir; Guo, Ke; Dharmarajan, Arun; Bielke, Wolfgang; Artuso, Livia; Saurer, Susanne; Friis, Robert R.

doi:10.1016/s0014-5793(97)01324-0

Cited by 67 publications

(51 citation statements)

References 25 publications

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“…We have previously shown that DDC-4/sFRP-4 was upregulated in various tissues undergoing physiological apoptosis. 3,4,45 The new data show that DDC-4/sFRP-4 expression is a stimulus rather than a consequence of the apoptotic program in the mammary gland. Since DDC-4 is an sFRP and thus thought to sequester Wnt ligands, we propose a role for DDC-4/sFRP-4 in abrogating a Wnt-regulated survival pathway, the latter possibly signaling via PKB/Akt.…”

Section: Discussionmentioning

confidence: 81%

“…4 The retroviral construct is shown schematically in Figure 1a. Using the BOSC 'helper' packaging cells, 16 retroviral titres of 2 Â 10 5 infectious units/ml were obtained.…”

Section: Establishment Of Cell Lines Overexpressing Ddc-4/ Sfrp-4mentioning

confidence: 99%

“…4 Because of the absence of suitable restriction enzyme sites that would allow the coding information to be cloned into the pBabe puro vector without extensive 5 0 and 3 0 untranslated regions, we used PCR to obtain a subfragment spanning the coding sequence associated with short (20-30 bp) 5 0 and 3 0 untranslated regions. The primers were constructed to contain restriction enzyme sites near their 5 0 termini, BamH1 for the sense, and EcoRI for the antisense primers.…”

Section: Construction Of the Ddc-4/sfrp-4 Retroviral Vectormentioning

confidence: 99%

“…3 One of the most interesting genes isolated, DDC-4, showed striking homology to the ligand-binding domain of several frizzled family, 7-pass transmembrane receptors. DDC-4 was subsequently recognized as encoding a product belonging to the secreted frizzled-related protein (sFRP) subfamily, 4 and is referred to here as DDC-4/sFRP-4.…”

Section: Introductionmentioning

confidence: 99%

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Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution

et al. 2003

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Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3b (GSK-3b), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.

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Section: Discussionmentioning

confidence: 81%

“…4 The retroviral construct is shown schematically in Figure 1a. Using the BOSC 'helper' packaging cells, 16 retroviral titres of 2 Â 10 5 infectious units/ml were obtained.…”

Section: Establishment Of Cell Lines Overexpressing Ddc-4/ Sfrp-4mentioning

confidence: 99%

Section: Construction Of the Ddc-4/sfrp-4 Retroviral Vectormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution

et al. 2003

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“…Secretory Frps were independently isolated from bovine, Xenopus, mouse, rat and human by different laboratories (Hoang et al, 1996; Leyns et al, 1997; Rattner et al, 1997;Wang et al, 1997;Wolf et al, 1997;Zhou et al, 1998;Chang et al, 1999;Yam et al, 1999;Katoh, 2001). The precise interaction of each Frp protein in modulating Wnt signaling remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of the promoter of the rat frizzled related protein gene by CREB

2003

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Frizzled related proteins (Frps) are secreted proteins structurally similar to frizzled receptors; they bind Wnt via the cysteine-rich domain and antagonize the Wnt signaling pathway. In this study, we have investigated the mechanisms regulating the transcriptional regulation of rat Frp (rFrp) promoter. From previous findings, we know that the transcriptional activation domain of rFrp resides in the region À202 to À144 relative to the transcription start site, and that it is essential for efficient promoter activity. The study presented here was designed to identify trans-acting factors that bind to this critical domain of the rFrp promoter and to elucidate the pathway involved in the regulation of rFrp expression. Electrophoretic mobility shift assay (EMSA) demonstrated that specific DNAprotein binding activities fall into two adjacent core sequences with (CTTTGGGGG) at À197 to À189 and (AGATGATGTAA) at À151 to À141 of the rFrp promoter. Reporter assay showed that these core sequences are both required for the activation of rFrp promoter. Mutation within either one or both core sequence drastically reduced the promoter activity. Southwestern blotting showed that the estimated molecular mass of the distinct binding protein to the (AGATGATG-TAA) domain is about 43 kDa. Further EMSA suggested CREB as the trans-acting factor in the DNA-protein complex, which was out competed by CREB consensus oligonucleotides and supershifted by anti-CREB antibody. Overexpression of PKA and CREB also transactivated rFrp promoter, and dominant-negative CREB inhibited the promoter activity in transient reporter assays. More importantly, CREB, phosphorylated CREB and the adaptor protein CBP were found binding to the endogenous rFrp promoter using chromatin immunoprecipitation assay. Collectively, our results demonstrate the induction of rFrp promoter activity by PKA and CREB in vitro, and the binding of CREB and CBP to the rFrp promoter core motif in vivo.

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Secreted Frizzled‐related proteins: searching for relationships and patterns

2002

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Secreted Frizzled-related proteins (SFRPs) are modulators of the intermeshing pathways in which signals are transduced by Wnt ligands through Frizzled (Fz) membrane receptors. The Wnt networks influence biological processes ranging from developmental cell fate, cell polarity and adhesion to tumorigenesis and apoptosis. In the five or six years since their discovery, the SFRPs have emerged as dynamically expressed proteins able to bind both Wnts and Fz, with distinctive structural properties in which cysteine-rich domains from Fz- and from netrin-like proteins are juxtaposed. The abundant expression of SFRP genes in the early embryo, altered expression patterns in disease states, and potential significance in the evolution of the vertebrate body plan, make these intriguing molecules relevant to investigations in diverse fields of biology and biomedical sciences.

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DDC‐4, an apoptosis‐associated gene, is a secreted frizzled relative

Cited by 67 publications

References 25 publications

Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution

Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution

Transcriptional regulation of the promoter of the rat frizzled related protein gene by CREB

Secreted Frizzled‐related proteins: searching for relationships and patterns

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