Vertebrate tankyrase domain structure and sterile α motif (SAM)-mediated multimerization

Manu De Rycker, Ranga N. Venkatesan, Chao Wei, Carolyn M. Price

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

Abstract

Tankyrases 1 and 2 are two highly related poly(ADP-ribose) polymerases that interact with a variety of cytoplasmic and nuclear proteins. Both proteins have been implicated in telomere length regulation, insulin signalling and centrosome function. To learn more about their mode of action, we have isolated the chicken tankyrase homologues and examined their interaction partners and subcellular location. Cross-species sequence comparison indicated that tankyrase domain structure is highly conserved and supports division of the ankyrin domain into five subdomains, which are each separated by a highly conserved LLEAAR/K motif. Glutathione S-transferase pulldown experiments demonstrated that the ankyrin domains of both proteins interact with chicken telomere repeat factor 1 (TRF1). Analysis of total cellular and nuclear proteins revealed that cells contain approximately twice as much tankyrase 1 as tankyrase 2. Although ≥ 90% of each protein is present in the cytoplasm, both tankyrase 1 and 2 were detected in the nucleus. The nuclear location together with its ability to interact with TRF1, point to tankyrase 2 having a telomeric function. Yeast two-hybrid and cross-linking experiments show that both tankyrases can multimerize through their sterile-α motif domains. These results indicate that tankyrases may be master scaffolding proteins, capable of regulating assembly of large protein complexes.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalBiochemical Journal
Volume372
Issue number1
DOIs
Publication statusPublished - 15 May 2003

Keywords

  • Chicken
  • Insulin signalling
  • Poly(ADP-ribose) polymerase (PARP)
  • Telomere
  • Telomere repeat factor 1 (TRF1)

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