Tankyrase: a promising therapeutic target with pleiotropic action.
Vrunda SagathiaChirag Amrutlal PatelJayesh BeladiyaSandip PatelDevang ShethGaurang ShahPublished in: Naunyn-Schmiedeberg's archives of pharmacology (2023)
Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) enzymes belong to the poly (ADP-ribose) polymerase (PARP) family participates in process of poly-ADP-ribosylation of different target proteins which leads to ubiquitin-mediated proteasomal degradation. Tankyrases are also involved in the pathophysiology of many diseases, especially cancer. Their functions include cell cycle homeostasis (primarily in mitosis), telomere maintenance, Wnt signaling pathway regulation, and insulin signaling (particularly GLUT4 translocation). Studies have implicated that genetic changes, mutations in the tankyrase coding sequence, or up regulation and down regulation of tankyrase are reflected in the numerous disease conditions. Investigations are pursued to develop putative molecules that target tankyrase in various diseases such as cancer, obesity, osteoarthritis, fibrosis, cherubism, and diabetes, thereby providing a new therapeutic treatment option. In the present review, we described the structure and function of tankyrase along with its role in different disease conditions. Furthermore, we also presented cumulative experimental evidences of different drugs acting on tankyrase.
Keyphrases
- cell cycle
- type diabetes
- papillary thyroid
- signaling pathway
- cell proliferation
- insulin resistance
- stem cells
- metabolic syndrome
- small molecule
- adipose tissue
- weight loss
- body mass index
- knee osteoarthritis
- glycemic control
- rheumatoid arthritis
- young adults
- epithelial mesenchymal transition
- oxidative stress
- skeletal muscle
- copy number
- smoking cessation
- childhood cancer