Question

What is the role of DKK?

Answer 1

Answer:

First let us see what are Dickkopf (Dkk) proteins.

Dkk family proteins are important regulators of the Wnt/β-catenin signaling pathway, which plays key roles in many essential biological processes and in a variety of disease, including cardiovascular diseases.

Lets us see what is Wnt/β-catenin signaling pathway:

“Wnt” is a combination of Wg (wingless) gene in Drosophila and Int gene in MMTV, two homologous genes. Wnt are secreted proteins. There are 19 Wnt genes in humans and mice. The Wnt1 gene, originally named Int-1, was identified in 1982 as a gene activated by integration of mouse mammary tumor virus proviral DNA in virally induced breast tumors.

β-Catenin: A multifunctional protein that plays an important role in the transduction of Wnt signals and in the intercellular adhesion by linking the cytoplasmic domain of cadherin.

Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal.

Lets us see what are Dkk proteins and physioloical roles.

Wnt signaling is characterized by a large number of ligands, receptors, and coreceptors and can be regulated at many different levels. Among Wnt modulators, the evolutionary conserved Dkk proteins, and especially Dkk-1, the founding member of the family, are the best characterized.

The role of Dkks in the pathophysiology of the arterial wall is partially understood, however, their role in atherosclerosis is becoming progressiively evident.

Roles of Dkk

• Dkk family proteins are vital regulators of the Wnt/β-catenin signaling pathway, which inturn plays key roles in many essential biological processes and in a variety of disease, including cardiovascular diseases.
• In addition to modulating the canonical Wnt pathway, Dkks can also involved with non canonical Wnt signaling and exert Wnt-independent activities.
• These proteins, in particular Dkk-1 have important contributions to the development of atherosclerosis.
• Dkk-1 is a promising biomarker candidate for a better stratification of patients at high cardiovascular risk and a novel target of the statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases.

Summary: Dkk proteins regulate Wnt signaling as well as Wnt-independent pathways. The regulation of Dkk protein function is an important contributor of several human diseases. Currently, the role of these proteins in atherosclerosis is not completely understood, however, their involvement in the pathophysiology of the arterial wall is becoming progressively evident, which provides a rationale to address Dkk-targeted therapies for atheroprotection.