Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2003 May 15;372(Pt 1):87–96. doi: 10.1042/BJ20021450

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

Manu De Rycker 1, Ranga N Venkatesan 1, Chao Wei 1, Carolyn M Price 1
PMCID: PMC1223374  PMID: 12589701

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 pull-down 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 > or = 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-alpha motif domains. These results indicate that tankyrases may be master scaffolding proteins, capable of regulating assembly of large protein complexes.

Full Text

The Full Text of this article is available as a PDF (399.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Broccoli D., Chong L., Oelmann S., Fernald A. A., Marziliano N., van Steensel B., Kipling D., Le Beau M. M., de Lange T. Comparison of the human and mouse genes encoding the telomeric protein, TRF1: chromosomal localization, expression and conserved protein domains. Hum Mol Genet. 1997 Jan;6(1):69–76. doi: 10.1093/hmg/6.1.69. [DOI] [PubMed] [Google Scholar]
  2. Chi N. W., Lodish H. F. Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. J Biol Chem. 2000 Dec 8;275(49):38437–38444. doi: 10.1074/jbc.M007635200. [DOI] [PubMed] [Google Scholar]
  3. Chong L., van Steensel B., Broccoli D., Erdjument-Bromage H., Hanish J., Tempst P., de Lange T. A human telomeric protein. Science. 1995 Dec 8;270(5242):1663–1667. doi: 10.1126/science.270.5242.1663. [DOI] [PubMed] [Google Scholar]
  4. Cook Brandoch D., Dynek Jasmin N., Chang William, Shostak Grigoriy, Smith Susan. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol Cell Biol. 2002 Jan;22(1):332–342. doi: 10.1128/MCB.22.1.332-342.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. D'Amours D., Desnoyers S., D'Silva I., Poirier G. G. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999 Sep 1;342(Pt 2):249–268. [PMC free article] [PubMed] [Google Scholar]
  6. Gossen M., Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547–5551. doi: 10.1073/pnas.89.12.5547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jousset C., Carron C., Boureux A., Quang C. T., Oury C., Dusanter-Fourt I., Charon M., Levin J., Bernard O., Ghysdael J. A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein. EMBO J. 1997 Jan 2;16(1):69–82. doi: 10.1093/emboj/16.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kaminker P. G., Kim S. H., Taylor R. D., Zebarjadian Y., Funk W. D., Morin G. B., Yaswen P., Campisi J. TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. J Biol Chem. 2001 Jul 13;276(38):35891–35899. doi: 10.1074/jbc.M105968200. [DOI] [PubMed] [Google Scholar]
  9. Kim C. A., Phillips M. L., Kim W., Gingery M., Tran H. H., Robinson M. A., Faham S., Bowie J. U. Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression. EMBO J. 2001 Aug 1;20(15):4173–4182. doi: 10.1093/emboj/20.15.4173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kim Chongwoo A., Gingery Mari, Pilpa Rosemarie M., Bowie James U. The SAM domain of polyhomeotic forms a helical polymer. Nat Struct Biol. 2002 Jun;9(6):453–457. doi: 10.1038/nsb802. [DOI] [PubMed] [Google Scholar]
  11. Konrad J. P., Mills W., Easty D. J., Farr C. J. Cloning and characterisation of the chicken gene encoding the telomeric protein TRF2. Gene. 1999 Oct 18;239(1):81–90. doi: 10.1016/s0378-1119(99)00374-1. [DOI] [PubMed] [Google Scholar]
  12. Kuimov A. N., Kuprash D. V., Petrov V. N., Vdovichenko K. K., Scanlan M. J., Jongeneel C. V., Lagarkova M. A., Nedospasov S. A. Cloning and characterization of TNKL, a member of tankyrase gene family. Genes Immun. 2001 Feb;2(1):52–55. doi: 10.1038/sj.gene.6363722. [DOI] [PubMed] [Google Scholar]
  13. Li B., Oestreich S., de Lange T. Identification of human Rap1: implications for telomere evolution. Cell. 2000 May 26;101(5):471–483. doi: 10.1016/s0092-8674(00)80858-2. [DOI] [PubMed] [Google Scholar]
  14. Lyons R. J., Deane R., Lynch D. K., Ye Z. S., Sanderson G. M., Eyre H. J., Sutherland G. R., Daly R. J. Identification of a novel human tankyrase through its interaction with the adaptor protein Grb14. J Biol Chem. 2001 Feb 22;276(20):17172–17180. doi: 10.1074/jbc.M009756200. [DOI] [PubMed] [Google Scholar]
  15. Monz D., Munnia A., Comtesse N., Fischer U., Steudel W. I., Feiden W., Glass B., Meese E. U. Novel tankyrase-related gene detected with meningioma-specific sera. Clin Cancer Res. 2001 Jan;7(1):113–119. [PubMed] [Google Scholar]
  16. Peterson A. J., Kyba M., Bornemann D., Morgan K., Brock H. W., Simon J. A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions. Mol Cell Biol. 1997 Nov;17(11):6683–6692. doi: 10.1128/mcb.17.11.6683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ponting C. P. SAM: a novel motif in yeast sterile and Drosophila polyhomeotic proteins. Protein Sci. 1995 Sep;4(9):1928–1930. doi: 10.1002/pro.5560040927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Potter M. D., Buijs A., Kreider B., van Rompaey L., Grosveld G. C. Identification and characterization of a new human ETS-family transcription factor, TEL2, that is expressed in hematopoietic tissues and can associate with TEL1/ETV6. Blood. 2000 Jun 1;95(11):3341–3348. [PubMed] [Google Scholar]
  19. Sbodio Juan I., Chi Nai-Wen. Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner. J Biol Chem. 2002 Jun 21;277(35):31887–31892. doi: 10.1074/jbc.M203916200. [DOI] [PubMed] [Google Scholar]
  20. Sbodio Juan I., Lodish Harvey F., Chi Nai-Wen. 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):451–459. doi: 10.1042/0264-6021:3610451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schultz J., Ponting C. P., Hofmann K., Bork P. SAM as a protein interaction domain involved in developmental regulation. Protein Sci. 1997 Jan;6(1):249–253. doi: 10.1002/pro.5560060128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sedgwick S. G., Smerdon S. J. The ankyrin repeat: a diversity of interactions on a common structural framework. Trends Biochem Sci. 1999 Aug;24(8):311–316. doi: 10.1016/s0968-0004(99)01426-7. [DOI] [PubMed] [Google Scholar]
  23. Seimiya Hiroyuki, Smith Susan. The telomeric poly(ADP-ribose) polymerase, tankyrase 1, contains multiple binding sites for telomeric repeat binding factor 1 (TRF1) and a novel acceptor, 182-kDa tankyrase-binding protein (TAB182). J Biol Chem. 2002 Feb 19;277(16):14116–14126. doi: 10.1074/jbc.M112266200. [DOI] [PubMed] [Google Scholar]
  24. Sheng M., Kim E. The Shank family of scaffold proteins. J Cell Sci. 2000 Jun;113(Pt 11):1851–1856. doi: 10.1242/jcs.113.11.1851. [DOI] [PubMed] [Google Scholar]
  25. Smalla M., Schmieder P., Kelly M., Ter Laak A., Krause G., Ball L., Wahl M., Bork P., Oschkinat H. Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites. Protein Sci. 1999 Oct;8(10):1954–1961. doi: 10.1110/ps.8.10.1954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith S., Giriat I., Schmitt A., de Lange T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science. 1998 Nov 20;282(5393):1484–1487. doi: 10.1126/science.282.5393.1484. [DOI] [PubMed] [Google Scholar]
  27. Smith S. The world according to PARP. Trends Biochem Sci. 2001 Mar;26(3):174–179. doi: 10.1016/s0968-0004(00)01780-1. [DOI] [PubMed] [Google Scholar]
  28. Smith S., de Lange T. Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes. J Cell Sci. 1999 Nov;112(Pt 21):3649–3656. doi: 10.1242/jcs.112.21.3649. [DOI] [PubMed] [Google Scholar]
  29. Smith S., de Lange T. Tankyrase promotes telomere elongation in human cells. Curr Biol. 2000 Oct 19;10(20):1299–1302. doi: 10.1016/s0960-9822(00)00752-1. [DOI] [PubMed] [Google Scholar]
  30. Thanos C. D., Bowie J. U. p53 Family members p63 and p73 are SAM domain-containing proteins. Protein Sci. 1999 Aug;8(8):1708–1710. doi: 10.1110/ps.8.8.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thanos C. D., Goodwill K. E., Bowie J. U. Oligomeric structure of the human EphB2 receptor SAM domain. Science. 1999 Feb 5;283(5403):833–836. doi: 10.1126/science.283.5403.833. [DOI] [PubMed] [Google Scholar]
  32. Tu H., Barr M., Dong D. L., Wigler M. Multiple regulatory domains on the Byr2 protein kinase. Mol Cell Biol. 1997 Oct;17(10):5876–5887. doi: 10.1128/mcb.17.10.5876. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES