The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

Lee, Soung Hoon; Kim, Mi Yeon; Kim, Hyun Yi; Lee, Young Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik; Chung, Kee Yang; Choi, Kang Yell

doi:10.1084/jem.20141601

Cited by 51 publications

(61 citation statements)

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“…Apart from being a transcription factor, CXXC5 was shown to act as a negative-feedback regulator of Wnt/β-catenin signaling by interacting with the cytoplasmic scaffold Dishevelled (Dvl) proteins in osteoblast differentiation and bone formation33, cutaneous wound healing and collagen production34, neural stem cell differentiation and telencephalon development13. CXXC5 was also reported to interact with and require for DNA damage-induced ATM phosphorylation, subsequent activation of p53, cell cycle arrest and apoptosis35.…”

Section: Discussionmentioning

confidence: 99%

Estradiol-Estrogen Receptor α Mediates the Expression of the CXXC5 Gene through the Estrogen Response Element-Dependent Signaling Pathway

Yaşar

Ayaz

Muyan

2016

Sci Rep

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17β-estradiol (E2), the primary circulating estrogen hormone, mediates physiological and pathophysiological functions of breast tissue mainly through estrogen receptor α (ERα). Upon binding to E2, ERα modulates the expression of target genes involved in the regulation of cellular proliferation primarily through interactions with specific DNA sequences, estrogen response elements (EREs). Our previous microarray results suggested that E2-ERα modulates CXXC5 expression. Because of the presence of a zinc-finger CXXC domain (ZF-CXXC), CXXC5 is considered to be a member of the ZF-CXXC family, which binds to non-methylated CpG dinucleotides. Although studies are limited, CXXC5 appears to participate as a transcription factor, co-regulator and/or epigenetic factor in the regulation of cellular events induced by various signaling pathways. However, how signaling pathways mediate the expression of CXXC5 is yet unclear. Due to the importance of E2-ERα signaling in breast tissue, changes in the CXXC5 transcription/synthesis could participate in E2-mediated cellular events as well. To address these issues, we initially examined the mechanism whereby E2-ERα regulates CXXC5 expression. We show here that CXXC5 is an E2-ERα responsive gene regulated by the interaction of E2-ERα with an ERE present at a region upstream of the initial translation codon of the gene.

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Section: Discussionmentioning

confidence: 99%

Estradiol-Estrogen Receptor α Mediates the Expression of the CXXC5 Gene through the Estrogen Response Element-Dependent Signaling Pathway

Yaşar

Ayaz

Muyan

2016

Sci Rep

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“…For activation of canonical pathway, PDZ domain of DVL interacts with β-arrestin, Casein Kinase 1, Casein Kinase 2, Frizzled and Protein Phosphatase 2C [16, 43, 58–65]. On the other hand, proteins like IDAX, CXXC5, Notch, and Naked cuticle behave as antagonist and repress the Wnt pathway [36, 66–74] (see Table 1 and Figure 3). Similarly, the DEP domain associates with various activators (APC, diversion, protein kinase C) and antagonists (Gβγ Prickle) to regulate non-canonical pathway (see Table 1 and Figure 3).…”

Section: Dvl-associated Proteinsmentioning

confidence: 99%

Dishevelled: A masterful conductor of complex Wnt signals

Sharma

Castro‐Piedras

Simmons

et al. 2018

Cellular Signalling

153

146

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The Dishevelled gene was first identified in Drosophila mutants with disoriented hair and bristle polarity [1-3]. The Dsh gene (Dsh/Dvl, in Drosophila and vertebrates respectively) gained popularity when it was discovered that it plays a key role in segment polarity during early embryonic development in Drosophila [4]. Subsequently, the vertebrate homolog of Dishevelled genes were identified in Xenopus (Xdsh), mice (Dvl1, Dvl2, Dvl3), and in humans (DVL1, DVL2, DVL3) [5-10]. Dishevelled functions as a principal component of Wnt signaling pathway and governs several cellular processes including cell proliferation, survival, migration, differentiation, polarity and stem cell renewal. This review will revisit seminal discoveries and also summarize recent advances in characterizing the role of Dishevelled in both normal and pathophysiological settings.

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“…However, the authors did not quantify final scar size across treatment and control groups. (Lee, et al, 2015a)…”

Section: Recent Advances In Scarless Wound Healing Researchmentioning

confidence: 99%

Scarless wound healing: finding the right cells and signals

et al. 2016

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From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. Yet effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and oral mucosa. However, many new advances have occurred over recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have already demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches to diminishing scar formation (Fig. 1). Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be redirected to a more fetal, scarless phenotype.

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The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

Cited by 51 publications

References 50 publications

Estradiol-Estrogen Receptor α Mediates the Expression of the CXXC5 Gene through the Estrogen Response Element-Dependent Signaling Pathway

Estradiol-Estrogen Receptor α Mediates the Expression of the CXXC5 Gene through the Estrogen Response Element-Dependent Signaling Pathway

Dishevelled: A masterful conductor of complex Wnt signals

Scarless wound healing: finding the right cells and signals

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