Functional and structural diversity of the human Dickkopf gene family

Krupnik, Valery E.; Sharp, John; Jiang, Chian; Robison, Keith; Chickering, Troy W.; Amaravadi, Lakshmi; Brown, Diane E.; Guyot, Deborah J.; Mays, Gail G.; Leiby, Kevin R.; Chang, Belle; Duong, Thao; Goodearl, Andrew; Gearing, David P.; Sokol, Sergei Y.; McCarthy, S A

doi:10.1016/s0378-1119(99)00365-0

Cited by 440 publications

(447 citation statements)

References 34 publications

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“…Dkks are glycoproteins of 255-350 amino acids (aa) and a calculated MW between 24 and 29 kDa for Dkk1, 2 and -4 and 38 kDa for Dkk3. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis Xenopus Dkk1 secreted from oocytes and human Dkk1 produced in SK-LMS-1 and HEK 293T cells, have an apparent MW of 40, 35, and around 45 kDa, respectively (Glinka et al, 1998;Fedi et al, 1999;Krupnik et al, 1999). The protein is probably N-glycosylated at a single site at the N-terminus (Fedi et al, 1999;Krupnik et al, 1999).…”

Section: Physical Properties and Structure Of Dkk Proteinsmentioning

confidence: 99%

“…On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis Xenopus Dkk1 secreted from oocytes and human Dkk1 produced in SK-LMS-1 and HEK 293T cells, have an apparent MW of 40, 35, and around 45 kDa, respectively (Glinka et al, 1998;Fedi et al, 1999;Krupnik et al, 1999). The protein is probably N-glycosylated at a single site at the N-terminus (Fedi et al, 1999;Krupnik et al, 1999). This is supported by mass spectroscopy analysis where Xenopus Dkk1 immunoisolated from frog liver has a MW of 29237 þ /À34 Da, and is thus 373 Da larger than predicted for the full-length protein (C Kiecker, W-D Lehmann and CN, unpublished research).…”

Section: Physical Properties and Structure Of Dkk Proteinsmentioning

confidence: 99%

“…Thus, Dkks are an evolutionarily ancient gene family that was already present in the last common ancestor of cnidarians and bilaterians and which was probably secondarily lost during evolution in protostomes. A distant Dkk family member, soggy (sgy; also called Dickkopf-like protein 1 DKKL1), was described in vertebrates (Krupnik et al, 1999), which shows unique homology to Dkk3.…”

Section: Evolution Of Dkk Genesmentioning

confidence: 99%

“…(2) Soggy, the distant member of the Dkk family, shares sequence similarity with Dkk3 but not with other Dkks (Krupnik et al, 1999). The similarity is most pronounced outside the two conserved Dkk cysteine-rich domains, raising the possibility that the gene arose from an ancestral Dkk3 precursor.…”

Section: Evolution Of Dkk Genesmentioning

confidence: 99%

“…Dkk3 and sgy are divergent members of the Dkk family which do not seem to function in Wnt signaling (Glinka et al, 1998;Krupnik et al, 1999;Mao et al, 2001a). It was suggested that an N-terminally truncated Dkk3 encodes a substrate binding subunit, 'p29', of the type II iodothyronine 5 0 -deiodinase (D2) in rat (Leonard et al, 2000).…”

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Function and biological roles of the Dickkopf family of Wnt modulators

2006

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Section: Physical Properties and Structure Of Dkk Proteinsmentioning

confidence: 99%

Section: Physical Properties and Structure Of Dkk Proteinsmentioning

confidence: 99%

Section: Evolution Of Dkk Genesmentioning

confidence: 99%

Section: Evolution Of Dkk Genesmentioning

confidence: 99%

mentioning

confidence: 99%

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Function and biological roles of the Dickkopf family of Wnt modulators

2006

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Aberrant accumulation of Dickkopf 4 promotes tumor progression via forming the immune suppressive microenvironment in gastrointestinal stromal tumor

Wang

Zhuang

et al. 2019

Cancer Medicine

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Background Drug resistance and tumor recurrence are the major concerns in clinical practices of gastrointestinal stromal tumor (GIST), with the urgent requirement for exploring undiscovered pathways driving malignancy. To deal with these, recent studies have made many efforts to explore prognosis indicators and establish potential therapeutic targets. Methods Expression profiles of different risks of GISTs were described and abundant clinical evidences supported our findings in this study. Following exploration in vitro by cell experiments and verification in vivo using tumor microarray were taken to elucidate the underlying mechanism, which drove the malignancy in GIST. Results Dickkopf 4 (DKK4), as the canonical Wnt pathway antagonist, was unexpectedly and universally upregulated in high‐risk GISTs, and aberrant accumulation of DKK4 was closely correlated with poor prognosis. In addition, tumor‐derived DKK4 could decrease immune cells infiltration and activation in the tumor microenvironment, which decreased the antitumor effects in return. And this phenomenon was recurrent in human tumor specimens. Conclusions Our findings identified DKK4 as a proper tumor biomarker for prognosis predicting and recurrence monitoring, and suggested a novel immune‐escape mechanism driving malignancy in GIST, which might be a potential therapeutic target to improve the effects of canonical RTK therapy and combined immunotherapy.

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Dickkopf‐3 alters the morphological response to retinoic acid during neuronal differentiation of human embryonal carcinoma cells

Alfonso

Gorroño-Etxebarria

Rábano

et al. 2014

Developmental Neurobiology

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Dickkopf-3 (Dkk-3) and Dkkl-1 (Soggy) are secreted proteins of poorly understood function that are highly expressed in subsets of neurons in the brain. To explore their potential roles during neuronal development, we examined their expression in Ntera-2 (NT2) human embryonal carcinoma cells, which differentiate into neurons upon treatment with retinoic acid (RA). RA treatment increased the mRNA and protein levels of Dkk-3 but not of Dkkl-1. Ectopic expression of both Dkk-3 and Dkkl-1 induced apoptosis in NT2 cells. Gene silencing of Dkk-3 did not affect NT2 cell growth or differentiation but altered their response to RA in suspension cultures. RA treatment of NT2 cells cultured in suspension resulted in morphological changes that led to cell attachment and flattening out of cell aggregates. Although there were no significant differences in the expression levels of cell adhesion molecules in control and Dkk-3-silenced cells, this morphological response was not observed in Dkk-3-silenced cells. These findings suggest that Dkk-3 plays a role in the regulation of cell interactions during RA-induced neuronal differentiation.

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Functional and structural diversity of the human Dickkopf gene family

Cited by 440 publications

References 34 publications

Function and biological roles of the Dickkopf family of Wnt modulators

Function and biological roles of the Dickkopf family of Wnt modulators

Aberrant accumulation of Dickkopf 4 promotes tumor progression via forming the immune suppressive microenvironment in gastrointestinal stromal tumor

Dickkopf‐3 alters the morphological response to retinoic acid during neuronal differentiation of human embryonal carcinoma cells

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