Tankyrase-2 oligomerizes with tankyrase-1 and binds to both TRF1 (telomere-repeat-binding factor 1) and IRAP (insulin-responsive aminopeptidase)

Biochem J. 2002 Feb 1;361(Pt 3):451-9. doi: 10.1042/0264-6021:3610451.

Abstract

The poly(ADP-ribose) polymerase (PARP) tankyrase-1 contains an ankyrin-repeat domain that binds to various partners, including the telomeric protein TRF1 (telomere-repeat-binding factor 1) and the vesicular protein IRAP (insulin-responsive aminopeptidase). TRF1 binding recruits tankyrase-1 to telomeres and allows its PARP activity to regulate telomere homoeostasis. By contrast, IRAP binding and the Golgi co-localization of tankyrase-1 with IRAP might allow tankyrase-1 to affect the targeting of IRAP-containing vesicles. A closely related protein, tankyrase-2, has also been implicated in vesicular targeting. Unlike tankyrase-1, tankyrase-2 has not been shown to have PARP activity. In addition, it has not been implicated in telomere homoeostasis, because it did not interact with TRF1 in previous studies. Here we show that tankyrase-2 contains intrinsic PARP activity and, like tankryase-1, binds to both TRF1 and IRAP. Our analysis suggests that the ankyrin (ANK) domain of tankyrase-2 comprises five subdomains that provide redundant binding sites for IRAP. Moreover, tankyrase-2 associates and co-localizes with tankyrase-1, suggesting that both tankyrases might function as a complex. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Golgi Apparatus / metabolism
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / metabolism
  • Sequence Homology, Amino Acid
  • Sialoglycoproteins / chemistry
  • Sialoglycoproteins / metabolism*
  • Tankyrases*
  • Telomeric Repeat Binding Protein 1
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • DNA-Binding Proteins
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Sialoglycoproteins
  • Telomeric Repeat Binding Protein 1
  • Adenosine Diphosphate
  • RNA
  • Poly(ADP-ribose) Polymerases
  • TNKS2 protein, human
  • Tankyrases
  • TNKS protein, human