TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression.
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.
Kaminker
P G
PG
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Kim
S H
SH
Taylor
R D
RD
Zebarjadian
Y
Y
Funk
W D
WD
Morin
G B
GB
Yaswen
P
P
Campisi
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D038501:Tankyrases; D035321:Telomeric Repeat Binding Protein 1
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D035321:Telomeric Repeat Binding Protein 1; D011065:Poly(ADP-ribose) Polymerases; C437334:TNKS2 protein, human; D038501:Tankyrases