DVL3

DVL3

The protein structure of DVL3.

DVL3 (Dishevelled segment polarity protein 3) is a protein that plays a crucial role in the Wnt signaling pathway. It is a member of the Dishevelled (DVL) protein family, which consists of three highly conserved proteins: DVL1, DVL2, and DVL3. DVL3 is involved in various cellular processes, including embryonic development, tissue homeostasis, and cell proliferation.

Structure

The DVL3 protein consists of several domains that are important for its function. It contains an N-terminal DIX (Dishevelled and Axin) domain, which mediates protein-protein interactions and is essential for the activation of downstream signaling pathways. The DIX domain of DVL3 interacts with other proteins, such as Axin and GSK3β, to regulate the stability and activity of β-catenin, a key component of the Wnt signaling pathway.

In addition to the DIX domain, DVL3 also contains a PDZ (PSD-95/Discs large/ZO-1) domain, which is involved in protein-protein interactions and plays a role in the assembly of signaling complexes. The PDZ domain of DVL3 interacts with various proteins, including Frizzled receptors and other components of the Wnt signaling pathway, to facilitate signal transduction.

Function

DVL3 is a key regulator of the Wnt signaling pathway, which is essential for embryonic development and tissue homeostasis. In the absence of Wnt ligands, DVL3 forms a complex with Axin, GSK3β, and other proteins, leading to the phosphorylation and degradation of β-catenin. This prevents the accumulation of β-catenin in the cytoplasm and nucleus, thereby inhibiting the activation of Wnt target genes.

Upon binding of Wnt ligands to Frizzled receptors, DVL3 is recruited to the plasma membrane and undergoes conformational changes. This activates the DVL3 protein and promotes the formation of a signaling complex, which includes Axin, GSK3β, and other proteins. The activated DVL3 protein inhibits the phosphorylation and degradation of β-catenin, allowing it to accumulate in the cytoplasm and translocate to the nucleus. In the nucleus, β-catenin interacts with transcription factors to activate the expression of Wnt target genes, which are involved in various cellular processes.

Role in Development

DVL3 plays a critical role in embryonic development, particularly in the formation of various tissues and organs. Studies have shown that DVL3 is required for the proper development of the central nervous system, skeletal system, and cardiovascular system. It is involved in cell proliferation, differentiation, and migration, which are essential for the formation of these tissues.

Mutations in the DVL3 gene have been associated with several developmental disorders, including Robinow syndrome and autosomal dominant Robinow syndrome. These disorders are characterized by skeletal abnormalities, such as short stature, facial dysmorphism, and limb defects. The dysregulation of the Wnt signaling pathway due to DVL3 mutations disrupts normal embryonic development, leading to these developmental disorders.

Clinical Significance

DVL3 has also been implicated in various diseases, including cancer. Aberrant activation of the Wnt signaling pathway, often caused by mutations in DVL3 or other components of the pathway, is frequently observed in cancer cells. This dysregulation of the Wnt pathway contributes to tumor initiation, progression, and metastasis.

Targeting DVL3 and the Wnt signaling pathway has emerged as a potential therapeutic strategy for cancer treatment. Several inhibitors and modulators of the Wnt pathway are currently being developed and tested in preclinical and clinical studies. By specifically targeting DVL3 and its downstream signaling, it may be possible to inhibit tumor growth and improve patient outcomes.

See Also

• Wnt signaling pathway
• Dishevelled
• β-catenin
• Frizzled receptors
• Axin
• GSK3β