WD40-Repeat Proteins in Ciliopathies and Congenital Disorders of Endocrine System

Kim, Yeon Joo

doi:10.3803/enm.2020.302

Cited by 18 publications

(10 citation statements)

References 148 publications

(191 reference statements)

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“…By contrast, the Grl originally designated CG3831 has homologs across a wide range of Holozoa (i.e., animals and their closest single-celled, non-fungal relatives), including chordates (e.g., the lancelet Branchiostoma floridae ) and single-cell eukaryotes (e.g., Capsaspora owczarzaki ) (Figure 3—figure supplements 1-4), leading us to name it GrlHolozoa (GrlHz). A subset of GrlHz homologs bear a long N-terminal domain containing WD40 repeats, which form a structurally-predicted beta-propeller domain, which is typically involved in protein-protein interactions (Figure 3—figure supplement 1D) (Kim and Kim, 2020).…”

Section: Resultsmentioning

confidence: 99%

Structural screens identify candidate human homologs of insect chemoreceptors and crypticDrosophilagustatory receptor-like proteins

Benton

Himmel

2022

Preprint

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Insect Odorant receptors and Gustatory receptors define a superfamily of seven-transmembrane domain ligand-gated ion channels (termed here 7TMICs), with homologs identified across Animalia except Chordata. Recently, we used sequence-based screening methods to reveal conservation of this family in unicellular eukaryotes and plants (DUF3537 proteins) (Benton et al., 2020). Here we combine three-dimensional structure-based screening,ab initioprotein folding predictions, phylogenetics and expression analyses to characterize additional candidate homologs with tertiary but little or no primary structural similarity to known 7TMICs, including proteins in disease-causing Trypanosoma. Unexpectedly, we identify structural similarity between 7TMICs and PHTF proteins, a deeply-conserved family of unknown function, whose human orthologs display enriched expression in testis, cerebellum and muscle. We also discover divergent groups of 7TMICs in insects, which we term the Gustatory receptor-like (Grl) proteins. SeveralDrosophila melanogasterGrls display selective expression in subsets of taste neurons, suggesting that they are previously-unrecognized insect chemoreceptors. Although we cannot exclude the possibility of remarkable structural convergence, our findings support the origin of 7TMICs in a eukaryotic common ancestor, counter previous assumptions of complete loss of 7TMICs in Chordata, and highlight the extreme evolvability of this protein fold, which likely underlies its functional diversification in different cellular contexts.

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Section: Resultsmentioning

confidence: 99%

Structural screens identify candidate human homologs of insect chemoreceptors and crypticDrosophilagustatory receptor-like proteins

Benton

Himmel

2022

Preprint

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“…In addition, the WD40 repeat domain, one of the shared proteins, is normally expressed in eukaryotes and acts as a scaffold for protein–protein interactions . It is also involved in the regulation of chromatin assembly, cell cycle, and apoptosis and is associated with a variety of endocrine diseases and neurological diseases. , Surprisingly, a family of CSD proteins shared among transcription factors has been shown to mediate the development of inflammatory diseases as well as autoimmune diseases through IL-2 . These results all point to the possibility that BMSCs-Exos may have a positive effect on cartilage and bone injury, and our current results of BMSCs-Exos intervention in chondrocytes and CIA model rats confirm the above conjecture.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Rheumatoid Arthritis Symptoms via Shuttling Proteins

Wang,

Li,

Wang

et al. 2024

J. Proteome Res.

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Our prior investigations have evidenced that bone marrow mesenchymal stem cell (BMSC) therapy can significantly improve the outcomes of rheumatoid arthritis (RA). This study aims to conduct a comprehensive analysis of the proteomics between BMSCs and BMSCs-Exos, and to further elucidate the potential therapeutic effect of BMSCs-Exos on RA, so as to establish a theoretical framework for the prevention and therapy of BMSCs-Exos on RA. The 4D label-free LC-MS/MS technique was used for comparative proteomic analysis of BMSCs and BMSCs-Exos. Collageninduced arthritis (CIA) rat model was used to investigate the therapeutic effect of BMSCs-Exos on RA. Our results showed that some homology and differences were observed between BMSCs and BMSCs-Exos proteins, among which proteins highly enriched in BMSCs-Exos were related to extracellular matrix and extracellular adhesion. BMSCs-Exos can be taken up by chondrocytes, promoting cell proliferation and migration. In vivo results revealed that BMSCs-Exos significantly improved the clinical symptoms of RA, showing a certain repair effect on the injury of articular cartilage. In short, our study revealed, for the first time, that BMSCs-Exos possess remarkable efficacy in alleviating RA symptoms, probably through shuttling proteins related to cell adhesion and tissue repair ability in CIA rats, suggesting that BMSCs-Exos carrying expressed proteins may become a useful biomaterial for RA treatment.

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“…Citing a few researches made in cancers occurring in other sub-types, WD 40-Repeat Proteins in ciliopathies have shown cancer-associated PALB2 mutations cause the loss of its binding ability to BRCA2/RAD51C and biallelic mutations of PALB2 are associated with increased occurrence of childhood cancers. 13 FBXW7 is an ubiquitin ligase substrate receptor and most commonly deregulated ubiquitin proteasome system protein in human cancer. 14 The loss-of-function mutations in FBXW7 may result in inappropriate accumulation of cyclin E. These mutations are observed in 18% of colorectal cancers, 15% of uterine endometrial carcinoma and 40% of patients with uterine carcinosarcoma.…”

Section: Research Prospects In Ciliopathiesmentioning

confidence: 99%

Susceptibility of craniofacial ciliopathies to oral cancer-A proposed research

Kumar¹

2022

JDHODT

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The Ciliary disorders are a group of clinically and genetically overlapping disorders, manifesting as syndromes, whose patho-physiology arises due to defective ciliary function including its organelles. These are antenna-like organelles are present in the apical surface of numerous cell types in a variety of tissues and organs, in humans, currently under research in medico genetic field.1 During organogenesis, although the neural crest receives a significant amount of attention, craniofacial tissue has more patterning information present when compared to other tissues of the body.2 Newer studies have further indicated the importance of ciliary epithelia as a source of patterning information for the tissues in or-facial region. In this article, we propose a research in patients with craniofacial ciliopathies linking to origin of cancers in oro-facial region.

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WD40-Repeat Proteins in Ciliopathies and Congenital Disorders of Endocrine System

Cited by 18 publications

References 148 publications

Structural screens identify candidate human homologs of insect chemoreceptors and crypticDrosophilagustatory receptor-like proteins

Structural screens identify candidate human homologs of insect chemoreceptors and crypticDrosophilagustatory receptor-like proteins

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Rheumatoid Arthritis Symptoms via Shuttling Proteins

Susceptibility of craniofacial ciliopathies to oral cancer-A proposed research

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