Dishevelled (DVL) proteins precisely control Wnt signaling pathways with many effectors. While substantial research has advanced our understanding of DVL's role in Wnt pathways, key questions regarding its regulatory mechanisms and interactions remain unresolved. Herein, we present the recent advances and perspectives on how DVL regulates signaling. The experimentally determined conserved domain structures of DVL in conjunction with AlphaFold-predicted structures are used to understand the DVL's role in Wnt signaling regulation. We also summarize the role of DVL in various diseases and provide insights into further directions for research on the DVL-mediated signaling mechanisms. These findings underscore the importance of DVL as a pharmaceutical target or biological marker in diseases, offering exciting potential for future biomedical applications.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592973PMC
http://dx.doi.org/10.3390/cells13221870DOI Listing

Publication Analysis

Top Keywords

wnt signaling
12
dvl's role
8
role wnt
8
signaling
5
dvl
5
structural functional
4
functional insights
4
insights dishevelled-mediated
4
wnt
4
dishevelled-mediated wnt
4

Similar Publications

Wnt (wingless-type MMTV integration site family) signaling is an evolutionary conserved system highly active during embryogenesis, but in adult hearts has low activities under normal conditions. It is essential for a variety of physiological processes including stem cell regeneration, proliferation, migration, cell polarity, and morphogenesis, thereby ensuring homeostasis and regeneration of cardiac tissue. Its dysregulation and excessive activation during pathological conditions leads to morphological and functional changes in the heart resulting in impaired myocardial regeneration under pathological conditions such as myocardial infarction, heart failure, and coronary artery disease.

View Article and Find Full Text PDF

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation disorder of the gastrointestinal tract characterized by disrupted intestinal epithelial barrier function. Despite advances in treatment, including biological agents, achieving sustained remission remains challenging for many patients with IBD. This highlights the urgent need for novel therapeutic strategies.

View Article and Find Full Text PDF

The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression.

View Article and Find Full Text PDF

Breaking Left-Right Symmetry by the Interplay of Planar Cell Polarity, Calcium Signaling and Cilia.

Cells

December 2024

Laboratoire de Biologie du Développement, LBD, CNRS UMR7622, INSERM U1156, Sorbonne Université, F-75005 Paris, France.

The formation of the embryonic left-right axis is a fundamental process in animals, which subsequently conditions both the shape and the correct positioning of internal organs. During vertebrate early development, a transient structure, known as the left-right organizer, breaks the bilateral symmetry in a manner that is critically dependent on the activity of motile and immotile cilia or asymmetric cell migration. Extensive studies have partially elucidated the molecular pathways that initiate left-right asymmetric patterning and morphogenesis.

View Article and Find Full Text PDF

The Role and Mechanism of TRIM Proteins in Gastric Cancer.

Cells

December 2024

The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China.

Tripartite motif (TRIM) family proteins, distinguished by their N-terminal region that includes a Really Interesting New Gene (RING) domain with E3 ligase activity, two B-box domains, and a coiled-coil region, have been recognized as significant contributors in carcinogenesis, primarily via the ubiquitin-proteasome system (UPS) for degrading proteins. Mechanistically, these proteins modulate a variety of signaling pathways, including Wnt/β-catenin, PI3K/AKT, and TGF-β/Smad, contributing to cellular regulation, and also impact cellular activities through non-signaling mechanisms, including modulation of gene transcription, protein degradation, and stability via protein-protein interactions. Currently, growing evidence indicates that TRIM proteins emerge as potential regulators in gastric cancer, exhibiting both tumor-suppressive and oncogenic roles.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!