Tankyrase 2

Tankyrase 2 (TNKS2) is an enzyme that in humans is encoded by the TNKS2 gene. It is a member of the poly(ADP-ribose) polymerases (PARPs) family, which play a key role in various cellular processes such as DNA repair, Wnt signaling, and telomere maintenance. Tankyrase 2, along with Tankyrase 1, has been implicated in the regulation of β-catenin levels, thus influencing cell proliferation and growth.

Function

Tankyrase 2 is involved in several critical cellular functions. It has ADP-ribosylation activity, which modifies proteins by adding ADP-ribose polymers, affecting their function, localization, and interaction with other proteins. This modification is crucial for the regulation of telomere length and the maintenance of genomic stability. In the context of the Wnt/β-catenin signaling pathway, Tankyrase 2 targets various components for degradation, thereby regulating the levels of β-catenin, a key mediator of Wnt signaling. This pathway is essential for cell proliferation, differentiation, and embryonic development. Dysregulation of Wnt/β-catenin signaling has been linked to various diseases, including cancer.

Clinical Significance

The role of Tankyrase 2 in Wnt signaling and telomere maintenance makes it a potential target for therapeutic intervention in cancer and other diseases characterized by aberrant cell proliferation and genomic instability. Inhibitors of Tankyrase 2 are being explored as therapeutic agents, particularly in cancers where Wnt signaling is upregulated. Additionally, due to its role in telomere maintenance, Tankyrase 2 inhibitors might also be useful in the treatment of diseases related to telomere dysfunction.

Genetic and Molecular Biology

The TNKS2 gene is located on chromosome 10q23.31 and consists of multiple exons. The encoded protein, Tankyrase 2, contains an ankyrin repeat domain, which is involved in protein-protein interactions, and a PARP domain, responsible for its enzymatic activity. Mutations in the TNKS2 gene or dysregulation of Tankyrase 2 expression have been associated with various pathological conditions, although the full spectrum of its genetic contributions to disease is still under investigation.

Research Directions

Research on Tankyrase 2 is focused on elucidating its precise roles in cellular processes and disease, developing specific inhibitors as potential therapeutic agents, and understanding the implications of its inhibition in normal and disease states. Studies are also directed towards identifying the full range of Tankyrase 2 substrates and interacting partners to better understand its function and regulation.

See Also

• Poly(ADP-ribose) polymerase
• Wnt signaling pathway
• Telomere
• β-Catenin

External Links

• TNKS2 gene on NCBI