Disease relevance of TNKS2

• Tankyrase 2 deficiency did result in a significant decrease in body weight sustained through at least the first year of life, most marked in male mice, suggesting that tankyrase 2 functions in potentially telomerase-independent pathways to affect overall development and/or metabolism [1].
• The anaplastic meningioma sera did not identify any tankyrase-related clones [2].
• By serological screening of a breast tumor cDNA library we have identified a novel human gene, tnkl, encoding an ankyrin-related protein with a high degree of similarity to tankyrase, the poly(ADP-ribose)polymerase associated with human telomeres (Smith et al, Science 282: 1484) [3].
• However, review of a surgical specimen taken three years before for chronic paranasal sinusitis revealed an overlooked nasal T/NK cell lymphoma (TNKL), which showed similar histomorphology and immunophenotype with the CNS disease [4].

High impact information on TNKS2

• We show here by overexpression studies that tankyrase 2, like its closely related homolog tankyrase 1, can function as a positive regulator of telomere length in human cells, dependent on its catalytic PARP activity [5].
• Generation and characterization of telomere length maintenance in tankyrase 2-deficient mice [1].
• Tankyrase 2 poly(ADP-ribose) polymerase domain-deleted mice exhibit growth defects but have normal telomere length and capping [5].
• In the present study, we have assessed the in vivo function of mouse tankyrase 2 by germ line gene inactivation and show that inactivation of tankyrase 2 does not result in detectable alteration in telomere length when monitored through multiple generations of breeding [1].
• Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres [6].

Biological context of TNKS2

• TANK2 is encoded by a 66-kilobase pair gene (TNKS2) containing 28 exons, which express a 6.7-kilobase pair mRNA and a 1166-amino acid protein [7].
• The TANKYRASE 2 gene localizes to chromosome 10q23.2 and is widely expressed, with mRNA transcripts particularly abundant in skeletal muscle and placenta [8].
• In contrast to TANK1, however, TANK2 caused rapid cell death when highly overexpressed [7].
• In vivo, TANK2 may differ from TANK1 in its intrinsic or regulated PARP activity or its substrate specificity [7].
• Taken together, our findings indicate that tankyrase-1 and tankyrase-2 interact with the same set of proteins and probably mediate overlapping functions, both at telomeres and in vesicular compartments [9].

Anatomical context of TNKS2

• Upon subcellular fractionation, both Grb14 and tankyrase 2 associate with the low density microsome fraction, and association of these proteins in vivo can be detected by co-immunoprecipitation analysis [8].
• TANK2-induced death featured loss of mitochondrial membrane potential, but not PARP1 cleavage, suggesting that TANK2 kills cells by necrosis [7].
• Tankyrase 2 was also revealed in epithelial cells of a limited number of normal renal tubules, whereas other renal tissues were negative [10].
• To determine whether the up-regulation of tankyrase 2 is associated with tissue regeneration and cell proliferation, we compared the activity and concentration of the enzyme in a model human embryonic kidney cell line 293 arrested by serum deprivation and restimulated with serum [10].
• We propose that: 1. a locally silent "quiescent" form of nasal TNKL may exist; and 2. a thorough examination and even blind biopsy of the nasal cavity is indicated when primary T/NK-cell CNSL is diagnosed [4].

Physical interactions of TNKS2

• TANK2 interacted with TRF1 in yeast and in vitro and localized predominantly to a perinuclear region, similar to the properties of TANK1 [7].

Analytical, diagnostic and therapeutic context of TNKS2

• An antibody was generated by using synthetic peptide specific for tankyrase 2 and was tested by Western blot and immunocytochemically; no cross-reaction with isoenzyme 1 was revealed [10].

References