Tankyrase

The Tankyrases (TNKS1/PARP5A and TNKS2/PARP5B) are poly (ADP-ribose) polymerases that catalyze the ADP-ribosylation of target proteins. TNKS' are involved in the regulation of Wnt/β-catenin signaling and have been implicated in the pathology of various forms of cancer.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
5775 AZ 6102
Potent TNKS1/2 inhibitor
4514 JW 55
Tankyrase inhibitor
5084 MN 64
Potent and selective tankyrase inhibitor
5049 TC-E 5001
Potent tankyrase inhibitor
4855 WIKI4
Potent tankyrase inhibitor
3748 XAV 939
Potent tankyrase inhibitor

The Tankyrases (TNKS1/PARP5A and TNKS2/PARP5B) are poly (ADP-ribose) polymerases that catalyze the ADP-ribosylation of target proteins. TNKS' are involved in the regulation of Wnt/β-catenin signaling and have been implicated in the pathology of various forms of cancer.

TNKS1 and TNKS2 consist of ankyrin repeats, a SAM domain, and a catalytic ARTD domain. Substrates bind to TNKS through the ankyrin repeats, whereas the SAM domain mediates TNKS multimerization. The ARTD domain catalyzes the conversion of NAD+ to nicotinamide and ADP-ribose, before ADP-ribose is covalently attached to a target substrate or ADP-ribose polymer. TNKS1 has been shown to have autocatalytic activity, whilst GDP-mannose-4,6-dehydratase (GMD) and Fanconi anemia group 2D protein can inhibit TNKS catalytic activity. Phosphorylation of TNKS may also modulate its activity, for example PLK1-mediated phosphorylation may result in TNKS stabilization.

The TNKS' are widely expressed and are involved in a number of physiological processes including, telomere homeostasis, mitotic spindle formation, glucose uptake and Wnt signaling. TNKS regulates Wnt signaling through the modulation of the β-catenin destruction complex, which targets β-catenin for proteasomal degradation. An essential component of the destruction complex is axin1, which is also a TNKS substrate. TNKS-mediated axin1 APD-ribosylation targets axin1 to the proteasome for degradation, decreasing the stability of the destruction complex. This increases free β-catenin levels in the cytoplasm and consequently enhances Wnt/β-catenin signaling and transcription.

TNKS has been implicated in various disease states including, cancer, viral infection and tissue fibrosis. TNKS1 and TNKS2 expression has been reported to be elevated in many types of cancer, with TNKS inhibition being shown to reduce proliferation of colon carcinoma cell lines. TNKS inhibition can also suppress oncogenic Wnt signaling, as inhibition of TNKS stabilizes axin and the destruction complex, therefore attenuating Wnt/β-catenin signaling.

Literature for Tankyrase

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis

Tankyrase Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
TNKS Human TNKS NM_003747 O95271
Mouse Tnks NM_175091 Q6PFX9
Rat Tnks NM_001106084 NP_001099554
TNKS2 Human TNKS2 NM_025235 Q9H2K2
Mouse Tnks2 NM_001163635 Q3UES3
Rat Tnks2 NM_001107607 NP_001101077