Kaminker P G, Kim S H, Taylor R D, Zebarjadian Y, Funk W D, Morin G B, Yaswen P, Campisi J
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
J Biol Chem. 2001 Sep 21;276(38):35891-9. doi: 10.1074/jbc.M105968200. Epub 2001 Jul 13.
Tankyrase (TANK1) is a human telomere-associated poly(ADP-ribose) polymerase (PARP) that binds the telomere-binding protein TRF1 and increases telomere length when overexpressed. Here we report characterization of a second human tankyrase, tankyrase 2 (TANK2), which can also interact with TRF1 but has properties distinct from those of TANK1. 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. The protein shares 85% amino acid identity with TANK1 in the ankyrin repeat, sterile alpha-motif, and PARP catalytic domains but has a unique N-terminal domain, which is conserved in the murine TNKS2 gene. TANK2 interacted with TRF1 in yeast and in vitro and localized predominantly to a perinuclear region, similar to the properties of TANK1. In contrast to TANK1, however, TANK2 caused rapid cell death when highly overexpressed. TANK2-induced death featured loss of mitochondrial membrane potential, but not PARP1 cleavage, suggesting that TANK2 kills cells by necrosis. The cell death was prevented by the PARP inhibitor 3-aminobenzamide. In vivo, TANK2 may differ from TANK1 in its intrinsic or regulated PARP activity or its substrate specificity.
端锚聚合酶（TANK1）是一种与人类端粒相关的聚（ADP - 核糖）聚合酶（PARP），它能结合端粒结合蛋白TRF1，过表达时可增加端粒长度。在此我们报道了第二种人类端锚聚合酶——端锚聚合酶2（TANK2）的特性，它也能与TRF1相互作用，但具有与TANK1不同的特性。TANK2由一个66千碱基对的基因（TNKS2）编码，该基因包含28个外显子，表达一种6.7千碱基对的mRNA和一个1166个氨基酸的蛋白质。该蛋白质在锚蛋白重复序列、无活性α基序和PARP催化结构域与TANK1有85%的氨基酸同源性，但有一个独特的N端结构域，在小鼠TNKS2基因中是保守的。TANK2在酵母和体外与TRF1相互作用，并且主要定位于核周区域，这与TANK1的特性相似。然而，与TANK1不同的是，TANK2高度过表达时会导致细胞快速死亡。TANK2诱导的细胞死亡特征为线粒体膜电位丧失，但没有PARP1裂解，这表明TANK2通过坏死杀死细胞。细胞死亡可被PARP抑制剂3 - 氨基苯甲酰胺阻止。在体内，TANK2在其内在的或受调控的PARP活性或其底物特异性方面可能与TANK1不同。
