Nutritional energy stimulates NAD+ production to promote tankyrase-mediated PARsylation in insulinoma cells.

The poly-ADP-ribosylation (PARsylation) activity of tankyrase (TNKS) regulates diverse physiological processes including energy metabolism and wnt/β-catenin signaling. This TNKS activity uses NAD+ as a co-substrate to post-translationally modify various acceptor proteins including TNKS itself. PARsylation by TNKS often tags the acceptors for ubiquitination and proteasomal degradation.

FOXO1 is an essential regulator of pluripotency in human embryonic stem cells.

Pluripotency of embryonic stem cells (ESCs) is defined by their ability to differentiate into three germ layers and derivative cell types and is established by an interactive network of proteins including OCT4 (also known as POU5F1; ref. 4), NANOG (refs 5, 6), SOX2 (ref. 7) and their binding partners.

Hypermetabolism, hyperphagia, and reduced adiposity in tankyrase-deficient mice.

Objective: Tankyrase (TNKS) is a Golgi-associated poly-ADP-ribose polymerase that is implicated in the regulation of GLUT4 trafficking in 3T3-L1 adipocytes. Its chromosomal locus 8p23.1 is linked to monogenic forms of diabetes in certain kindred.

Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase.

The glucose transporter GLUT4 and the aminopeptidase IRAP (insulin-responsive aminopeptidase) are the major cargo proteins of GSVs (GLUT4 storage vesicles) in adipocytes and myocytes. In the basal state, most GSVs are sequestered in perinuclear and other cytosolic compartments. Following insulin stimulation, GSVs undergo exocytic translocation to insert GLUT4 and IRAP into the plasma membrane.

Mitotic phosphorylation of tankyrase, a PARP that promotes spindle assembly, by GSK3.

The assembly and function of mitotic spindles require poly(ADP-ribosyl)ation of spindle components by tankyrase, a poly(ADP-ribose) polymerase that aggregates to spindle poles during mitosis. Tankyrase itself is phosphorylated during mitosis, but the kinases involved remain undefined. Herein we report that mitotic phosphorylation of tankyrase is abrogated in cells treated with the GSK3 inhibitors LiCl and indirubin.

Tankyrase recruitment to the lateral membrane in polarized epithelial cells: regulation by cell-cell contact and protein poly(ADP-ribosyl)ation.

PARsylation [poly(ADP-ribosyl)ation] of proteins is implicated in the regulation of diverse physiological processes. Tankyrase is a molecular scaffold with this catalytic activity and has been proposed as a regulator of vesicular trafficking on the basis, in part, of its Golgi localization in non-polarized cells. Little is known about tankyrase localization in polarized epithelial cells.

Tankyrase-1 overexpression reduces genotoxin-induced cell death by inhibiting PARP1.

Poly(ADP-ribose) polymerases or PARPs are a family of NAD(+)-dependent enzymes that modify themselves and other substrate proteins with ADP-ribose polymers. The founding member PARP 1 is localized predominantly in the nucleus and is activated by binding to DNA lesions. Excessive PARP 1 activation following genotoxin treatment causes NAD(+) depletion and cell death, whereas pharmacological PARP 1 inhibition protects cells from genotoxicity.