Protein partners of <scp>KCTD</scp> proteins provide insights about their functional roles in cell differentiation and vertebrate development

Skoblov, Mikhail; Marakhonov, Andrey V.; Marakasova, Ekaterina; Гуськова, А. А.; Chandhoke, Vikas; Birerdinc, Aybike; Baranova, Ancha

doi:10.1002/bies.201300002

Cited by 78 publications

(120 citation statements)

References 71 publications

(98 reference statements)

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“…KCTD20, KCTD18, KCTD19, and KCTD4 do not belong to these seven groups (Figure 1). The evolutionary tree of the KCTD family proteins is similar to the group that Skoblov M et al built [25]. We also suggest that homologous KCTD members may share similar functional roles in proliferation, transcription, protein degradation, regulation of G-protein coupled receptors and other molecular or biological processes.…”

Section: Introductionsupporting

confidence: 79%

The KCTD family of proteins: structure, function, disease relevance

2013

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The family of potassium channel tetramerizationdomain (KCTD) proteins consists of 26 members with mostly unknown functions. The name of the protein family is due to the sequence similarity between the conserved N-terminal region of KCTD proteins and the tetramerization domain in some voltage-gated potassium channels. Dozens of publications suggest that KCTD proteins have roles in various biological processes and diseases. In this review, we summarize the character of Bric-a-brack,Tram-track, Broad complex(BTB) of KCTD proteins, their roles in the ubiquitination pathway, and the roles of KCTD mutants in diseases. Furthermore, we review potential downstream signaling pathways and discuss future studies that should be performed.

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Section: Introductionsupporting

confidence: 79%

The KCTD family of proteins: structure, function, disease relevance

2013

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“…The domain plays a major role in protein-protein interaction, transcription repression and protein ubiquitination/degradation [21]–[23]. The N-terminal BTB/POZ domain exists in a class of KCTD family proteins with a significant sequence identity of K+ channel tetramerization domain, while the C-terminal domains are diversified [24]. For instance, the K+ channel regulator protein (KCNRG) in the KCTD family interacts with the T1 domains of Kv channels to regulate surface expression of Shaker-type potassium channels and reduce potassium currents [25].…”

Section: Introductionmentioning

confidence: 99%

KCTD1 Suppresses Canonical Wnt Signaling Pathway by Enhancing β-catenin Degradation

Chen

Wang

et al. 2014

PLoS ONE

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The canonical Wnt signaling pathway controls normal embryonic development, cellular proliferation and growth, and its aberrant activity results in human carcinogenesis. The core component in regulation of this pathway is β-catenin, but molecular regulation mechanisms of β-catenin stability are not completely known. Here, our recent studies have shown that KCTD1 strongly inhibits TCF/LEF reporter activity. Moreover, KCTD1 interacted with β-catenin both in vivo by co-immunoprecipitation as well as in vitro through GST pull-down assays. We further mapped the interaction regions to the 1-9 armadillo repeats of β-catenin and the BTB domain of KCTD1, especially Position Ala-30 and His-33. Immunofluorescence analysis indicated that KCTD1 promotes the cytoplasmic accumulation of β-catenin. Furthermore, protein stability assays revealed that KCTD1 enhances the ubiquitination/degradation of β-catenin in a concentration-dependent manner in HeLa cells. And the degradation of β-catenin mediated by KCTD1 was alleviated by the proteasome inhibitor, MG132. In addition, KCTD1-mediated β-catenin degradation was dependent on casein kinase 1 (CK1)- and glycogen synthase kinase-3β (GSK-3β)-mediated phosphorylation and enhanced by the E3 ubiquitin ligase β-transducin repeat-containing protein (β-TrCP). Moreover, KCTD1 suppressed the expression of endogenous Wnt downstream genes and transcription factor AP-2α. Finally, we found that Wnt pathway member APC and tumor suppressor p53 influence KCTD1-mediated downregulation of β-catenin. These results suggest that KCTD1 functions as a novel inhibitor of Wnt signaling pathway.

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“…The family is composed of over 20 genes/proteins in different vertebrate species and can be subdivided into seven subgroups on the basis of sequence similarity (Liu et al, 2013; Skoblov et al, 2013). A number of Kctd genes have been associated with human diseases, as summarized by Liu and colleagues (Liu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest

Wong¹,

Rebbert²,

Wang³

et al. 2016

Int. J. Dev. Biol.

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Neural crest (NC) development is controlled precisely by a regulatory network with multiple signaling pathways and the involvement of many genes. The integration and coordination of these factors are still incompletely understood. Overexpression of Wnt3a and the BMP antagonist Chordin in animal cap cells from Xenopus blastulae induces a large number of NC specific genes. We previously suggested that Potassium Channel Tetramerization Domain containing 15 (Kctd15) regulates NC formation by affecting Wnt signaling and the activity of transcription factor AP-2. In order to advance understanding of the function of Kctd15 during NC development, we performed DNA microarray assays in explants injected with Wnt3a and Chordin, and identify genes that are affected by overexpression of Kctd15. Among many genes identified we chose Duf domain containing protein 1(ddcp1), Platelet-Derived Growth Factor Receptor a (pdgfra), Complement factor properdin (cfp), Zinc Finger SWIM-Type Containing 5 (zswim5), and complement component 3 (C3) to examine their expression by whole mount in situ hybridization. Our work points to a possible role for Kctd15 in the regulation of NC formation and other steps in embryonic development.

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Protein partners of KCTD proteins provide insights about their functional roles in cell differentiation and vertebrate development

Cited by 78 publications

References 71 publications

The KCTD family of proteins: structure, function, disease relevance

The KCTD family of proteins: structure, function, disease relevance

KCTD1 Suppresses Canonical Wnt Signaling Pathway by Enhancing β-catenin Degradation

Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest

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