TNIK

TRAF2 and NCK-interacting protein kinase is an enzyme that in humans is encoded by the TNIK gene. TNIK is involved in various cellular processes, including signal transduction, gene transcription, and cytoskeletal organization. As an emerging area of therapeutic research, TNIK inhibitors have shown potential in addressing a range of diseases, including cancer, neurological disorders, and inflammatory conditions.

Structure

Germinal center kinases, such as TNIK, are characterized by an N-terminal kinase domain and a C-terminal GCK domain that serves a regulatory function.

Function

TNIK is a serine/threonine kinase that plays a central role in diverse cellular processes, most notably as a key regulator of the Wnt signaling pathway. TNIK is recruited to the promoters of Wnt target genes where it interacts with both β-catenin and TCF4; it phosphorylates TCF4 to enable TCF/LEF-dependent transcriptional activation of Wnt target genes, a function critical for cell proliferation and stem cell maintenance, especially in intestinal and cancerous tissues.

Interactions

TNIK has been shown to interact with KIAA0090, although the significance is unclear. TNIK has been shown to phosphorylate Gelsolin, a protein involved in F-actin depolymerisation thus inducing cytoskeletal changes.

Clinical significance

TNIK plays an important role in pulmonary fibrosis. TNIK inhibitors are used in the treatment of pulmonary fibrosis. TNIK has increasingly been of interest in research into the biology of ageing. Rentosertib, an investigational new drug targeting TNIK, was the subject of a phase 2a trial conducted in China, testing the drug in 71 IPF patients from July 2023 to June 2024, encompassing an administration period of 12 weeks.