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S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function

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Abstract

The CacyBP/SIP protein (S100A6 binding protein and Siah-1 interacting protein) was originally discovered in Ehrlich ascites tumor cells as a S100A6 (calcyclin) target (Filipek and Wojda in Biochem J 320:585–587, 1996; Filipek and Kuźnicki in J Neurochem 70(5):1793–1798, 1998) and later on as a Siah-1 interacting protein (Matsuzawa and Reed in Mol Cell 7(5):915–926, 2001). CacyBP/SIP binds several target proteins such as some calcium binding proteins of the S100 family (Filipek et al. in J Biol Chem 277(32):28848–28852, 2002), Skp1 (Matsuzawa and Reed in Mol Cell 7(5):915–926, 2001), tubulin (Schneider et al. in Biochim Biophys Acta 1773(11):1628–1636, 2007) and ERK1/2 (Kilanczyk et al. in Biochem Biophys Res Commun 380:54–59, 2009). Studies concerning distribution of CacyBP/SIP show that it is present in various tissues and that a particularly high level of CacyBP/SIP is observed in brain (Jastrzebska et al. in J Histochem Cytochem 48(9):1195–1202, 2000). Regarding the function of CacyBP/SIP, there are some reports suggesting its role in cellular processes such as ubiquitination, proliferation, differentiation, tumorigenesis, cytoskeletal rearrangement or regulation of transcription. This review describes the properties of CacyBP/SIP and summarizes all findings concerning its cellular function.

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References

  • Alonso AD, Grundke-Iqbal I, Barra HS et al (1997) Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau. Proc Natl Acad Sci USA 94(1):298–303

    Article  PubMed  CAS  Google Scholar 

  • Amson RB, Nemani M, Roperch JP et al (1996) Isolation of 10 differentially expressed cDNAs in p53-induced apoptosis: activation of the vertebrate homologue of the drosophila seven in absentia gene. Proc Natl Acad Sci USA 93(9):3953–3957

    Article  PubMed  CAS  Google Scholar 

  • Au KW, Kou CY, Woo AY et al (2006) Calcyclin binding protein promotes DNA synthesis and differentiation in rat neonatal cardiomyocytes. J Cell Biochem 98(3):555–566

    Article  PubMed  CAS  Google Scholar 

  • Bai C, Sen P, Hofmann K et al (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86(2):263–274

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharya S, Lee YT, Michowski W et al (2005) The modular structure of SIP facilitates its role in stabilizing multiprotein assemblies. Biochemistry 44(27):9462–9471

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Han G, Zhai H, Zhang F et al (2008) Expression and clinical significance of CacyBP/SIP in pancreatic cancer. Pancreatology 8(4–5):470–477

    Article  PubMed  Google Scholar 

  • Chim SS, Cheung SS, Tsui SK (2000) Differential gene expression of rat neonatal heart analyzed by suppression subtractive hybridization and expressed sequence tag sequencing. J Cell Biochem 80(1):24–36

    Article  PubMed  CAS  Google Scholar 

  • Connelly C, Hieter P (1996) Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression. Cell 86(2):275–285

    Article  PubMed  CAS  Google Scholar 

  • De Petris L, Orre LM, Kanter L et al (2009) Tumor expression of S100A6 correlates with survival of patients with stage I non-small-cell lung cancer. Lung Cancer 63(3):410–417

    Article  PubMed  Google Scholar 

  • Demir O, Kurnaz IA (2008) Wildtype Elk-1, but not a SUMOylation mutant, represses egr-1 expression in SH-SY5Y neuroblastomas. Neurosci Lett 437:20–24

    Article  PubMed  CAS  Google Scholar 

  • Filipek A, Kuźnicki J (1998) Molecular cloning and expression of a mouse brain cDNA encoding a novel protein target of calcyclin. J Neurochem 70(5):1793–1798

    Article  PubMed  CAS  Google Scholar 

  • Filipek A, Wojda U (1996) p30, a novel protein target of mouse calcyclin (S100A6). Biochem J 320:585–587

    PubMed  CAS  Google Scholar 

  • Filipek A, Jastrzebska B, Nowotny M et al (2002a) CacyBP/SIP, a calcyclin and Siah-1-interacting protein, binds EF-hand proteins of the S100 family. J Biol Chem 277(32):28848–28852

    Article  PubMed  CAS  Google Scholar 

  • Filipek A, Jastrzebska B, Nowotny M et al (2002b) Ca2+-dependent translocation of the calcyclin-binding protein in neurons and neuroblastoma NB-2a cells. J Biol Chem 277(23):21103–21109

    Article  PubMed  CAS  Google Scholar 

  • Filipek A, Schneider G, Mietelska A et al (2008) Age-dependent changes in neuronal distribution of CacyBP/SIP: comparison to tubulin and the tau protein. J Neural Transm 115(9):1257–1264

    Article  PubMed  CAS  Google Scholar 

  • Fukushima T, Zapata JM, Singha NC et al (2006) Critical function for SIP, a ubiquitin E3 ligase component of the beta-catenin degradation pathway, for thymocyte development and G1 checkpoint. Immunity 24(1):29–39

    Article  PubMed  CAS  Google Scholar 

  • Gounari F, Aifantis I, Khazaie K et al (2001) Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development. Nat Immunol 2(9):863–869

    Article  PubMed  CAS  Google Scholar 

  • Herington JL, Bi J, Martin JD et al (2007) Beta-catenin (CTNNB1) in the mouse uterus during decidualization and the potential role of two pathways in regulating its degradation. J Histochem Cytochem 55(9):963–974

    Article  PubMed  CAS  Google Scholar 

  • Jastrzebska B, Filipek A, Nowicka D et al (2000) Calcyclin (S100A6) binding protein (CacyBP) is highly expressed in brain neurons. J Histochem Cytochem 48(9):1195–1202

    Article  PubMed  CAS  Google Scholar 

  • Kilanczyk E, Filipek S, Jastrzebska B et al (2009) CacyBP/SIP binds ERK1/2 and affects transcriptional activity of Elk-1. Biochem Biophys Res Commun 380:54–59

    Article  PubMed  CAS  Google Scholar 

  • Kim YS, Ham BK, Paek KH et al (2006) An Arabidopsis homologue of human seven-in-absentia-interacting protein is involved in pathogen resistance. Moll Cells 21(3):389–394

    CAS  Google Scholar 

  • Kitagawa K, Skowyra D, Elledge SJ et al (1999) SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. Mol Cell 4(1):21–33

    Article  PubMed  CAS  Google Scholar 

  • Komatsu K, Kobune-Fujiwara Y, Andoh A et al (2000) Increased expression of S100A6 at the invading fronts of the primary lesion and liver metastasis in patients with colorectal adenocarcinoma. Br J Cancer 83(6):769–774

    Article  PubMed  CAS  Google Scholar 

  • Komatsu K, Murata K, Kameyama M et al (2002) Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases. Oncology 63(2):192–200

    Article  PubMed  CAS  Google Scholar 

  • Lee YT, Dimitrova YN, Schneider G et al (2008) Structure of the S100A6 complex with a fragment from the C-terminal domain of Siah-1 interacting protein: a novel mode for S100 protein target recognition. Biochemistry 47(41):10921–10932

    Article  PubMed  CAS  Google Scholar 

  • Li S, Li Y, Carthew RW et al (1997) Photoreceptor cell differentiation requires regulated proteolysis of the transcriptional repressor Tramtrack. Cell 90(3):469–478

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Stevens J, Rote CA et al (2001) Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol Cell 7(5):927–936

    Article  PubMed  CAS  Google Scholar 

  • Lowy AM, Clements WM, Bishop J et al (2006) β-Catenin/Wnt signaling regulates expression of the membrane type 3 matrix metalloproteinase in gastric cancer. Cancer Res 66(9):4734–4741

    Article  PubMed  CAS  Google Scholar 

  • Lustig B, Behrens J (2003) The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol 129(4):199–221

    PubMed  CAS  Google Scholar 

  • Matigian N, Windus L, Smith H et al (2007) Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway. Mol Psychiatry 12(9):815–825

    Article  PubMed  CAS  Google Scholar 

  • Matsuzawa SI, Reed JC (2001) Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol Cell 7(5):915–926

    Article  PubMed  CAS  Google Scholar 

  • Matsuzawa S, Takayama S, Froesch BA et al (1998) p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1. EMBO J 17(10):2736–2747

    Article  PubMed  CAS  Google Scholar 

  • Matsuzawa S, Li C, Ni CZ et al (2003) Structural analysis of Siah1 and its interactions with Siah-interacting protein (SIP). J Biol Chem 278(3):1837–1840

    Article  PubMed  CAS  Google Scholar 

  • Mezhybovska M, Wikström K, Ohd JF et al (2006) The inflammatory mediator leukotriene D4 induces beta-catenin signaling and its association with antiapoptotic Bcl-2 in intestinal epithelial cells. J Biol Chem 281(10):6776–6784

    Article  PubMed  CAS  Google Scholar 

  • Michetti F, Grilli Caiola M, Botti F et al (1992) Immunochemical and immunohistochemical detection of S-100-like immunoreactivity in spinach tissues. J Histochem Cytochem 40(6):839–843

    Article  PubMed  CAS  Google Scholar 

  • Ning X, Sun S, Hong L et al (2007) Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer. Mol Cancer Res 5(12):1254–1262

    Article  PubMed  CAS  Google Scholar 

  • Nowotny M, Bhattacharya S, Filipek A et al (2000) Characterization of the interaction of calcyclin (S100A6) and calcyclin-binding protein. J Biol Chem 275(40):31178–31182

    Article  PubMed  CAS  Google Scholar 

  • Nowotny M, Spiechowicz M, Jastrzebska B et al (2003) Calcium-regulated interaction of Sgt1 with S100A6 (calcyclin) and other S100 proteins. J Biol Chem 278(29):26923–26928

    Article  PubMed  CAS  Google Scholar 

  • Ohuchida K, Mizumoto K, Yu J et al (2007) S100A6 is increased in a stepwise manner during pancreatic carcinogenesis: clinical value of expression analysis in 98 pancreatic juice samples. Cancer Epidemiol Biomark Prev 16(4):649–654

    Article  CAS  Google Scholar 

  • Pircher TJ, Geiger JN, Zhang D et al (2001) Integrative signaling by minimal erythropoietin receptor forms and c-Kit. J Biol Chem 276(12):8995–9002

    Article  PubMed  CAS  Google Scholar 

  • Reese J, Das SK, Paria BC et al (2001) Global gene expression analysis to identify molecular markers of uterine receptivity and embryo implantation. J Biol Chem 276(47):44137–44145

    Article  PubMed  CAS  Google Scholar 

  • Sangkhathat S, Kusafuka T, Miao J et al (2006) In vitro RNA interference against beta-catenin inhibits the proliferation of pediatric hepatic tumors. Int J Oncol 28(3):715–722

    PubMed  CAS  Google Scholar 

  • Santelli E, Leone M, Li C et al (2005) Structural analysis of Siah1–Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex. J Biol Chem 280(40):34278–34287

    Article  PubMed  CAS  Google Scholar 

  • Sbroggiò M, Ferretti R, Percivalle E et al (2008) The mammalian CHORD-containing protein melusin is a stress response protein interacting with Hsp90 and Sgt1. FEBS Lett 582(13):1788–1794

    Article  PubMed  Google Scholar 

  • Schneider G, Nieznanski K, Kilanczyk E et al (2007) CacyBP/SIP interacts with tubulin in neuroblastoma NB2a cells and induces formation of globular tubulin assemblies. Biochim Biophys Acta 1773(11):1628–1636

    Article  PubMed  CAS  Google Scholar 

  • Sharrocks AD (2001) The ETS domain transcription factor family. Nat Rev Mol Cell Biol 2:827–837

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Hu W, Yin F et al (2004) Regulation of drug sensitivity of gastric cancer cells by human calcyclin-binding protein (CacyBP). Gastric Cancer 7(3):160–166

    Article  PubMed  CAS  Google Scholar 

  • Słomnicki LP, Nawrot B, Leśniak W (2009) S100A6 binds p53 and affects its activity. Int J Biochem Cell Biol 41(4):784–790

    Article  PubMed  Google Scholar 

  • Stradal TB, Gimona M (1999) Ca(2+)-dependent association of S100A6 (Calcyclin) with the plasma membrane and the nuclear envelope. J Biol Chem 274(44):31593–31596

    Article  PubMed  CAS  Google Scholar 

  • Sun S, Ning X, Liu J et al (2007) Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma. Biochem Biophys Res Commun 356(4):864–871

    Article  PubMed  CAS  Google Scholar 

  • Vanhoutte P, Nissen JL, Brug B, Gaspera BD et al (2001) Opposing role of Elk-1 and its brain-specific isoform, short Elk-1, in nerve growth factor-induced PC12 differentiation. J Biol Chem 276:5189–5196

    Article  PubMed  CAS  Google Scholar 

  • Vickers ER, Kasza A, Kurnaz IA, Seifert A et al (2004) Ternary complex factor-serum response factor complex-regulated gene activity is required for cellular proliferation and inhibition of apoptotic cell death. Mol Cell Biol 24:10340–10351

    Article  PubMed  CAS  Google Scholar 

  • Vimalachandran D, Greenhalf W, Thompson C et al (2005) High nuclear S100A6 (Calcyclin) is significantly associated with poor survival in pancreatic cancer patients. Cancer Res 65(8):3218–3225

    PubMed  CAS  Google Scholar 

  • Weterman MA, Stoopen GM, van Muijen GN et al (1992) Expression of calcyclin in human melanoma cell lines correlates with metastatic behavior in nude mic. Cancer Res 52(5):1291–1296

    PubMed  CAS  Google Scholar 

  • Wu J, Tan X, Peng X et al (2003) Translocation and phosphorylation of calcyclin binding protein during retinoic acid-induced neuronal differentiation of neuroblastoma SH-SY5Y cells. J Biochem Mol Biol 36(4):354–358

    Article  PubMed  CAS  Google Scholar 

  • Xia ZB, Dai MS, Magoulas C et al (2000) Differentially expressed genes during in vitro differentiation of murine embryonic stem cells transduced with a human erythropoietin receptor cDNA. J Hematother Stem Cell Res 9(5):651–658

    Article  PubMed  CAS  Google Scholar 

  • Yang YJ, Liu WM, Zhou JX et al (2006) Expression and hormonal regulation of calcyclin-binding protein (CacyBP) in the mouse uterus during early pregnancy. Life Sci 78(7):753–760

    Article  PubMed  CAS  Google Scholar 

  • Yang YQ, Zhang LJ, Dong H et al (2007) Upregulated expression of S100A6 in human gastric cancer. J Dig Dis 8(4):186–193

    Article  PubMed  CAS  Google Scholar 

  • Zhai H, Shi Y, Jin H et al (2008) Expression of calcyclin-binding protein/Siah-1 interacting protein in normal and malignant human tissues: an immunohistochemical survey. J Histochem Cytochem 56(8):765–772

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, You H, Liu F et al (2002) Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells. Cancer Lett 185:211–218

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. W. Lesniak for helpful discussion and critical reading of the manuscript. This work was supported by a grant to A. Filipek (2 P04A 01030) from the Ministry of Science and Higher Education of Poland and by statutory funds from the Nencki Institute of Experimental Biology.

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  1. Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093, Warsaw, Poland

    Gabriela Schneider & Anna Filipek

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  1. Gabriela Schneider
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  2. Anna Filipek
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Correspondence to Anna Filipek.

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Schneider, G., Filipek, A. S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function. Amino Acids 41, 773–780 (2011). https://doi.org/10.1007/s00726-010-0498-2

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