Molecular and Cellular Biochemistry

, Volume 275, Issue 1–2, pp 75–84 | Cite as

Characterization of Mesenchyme Homeobox 2 (MEOX2) transcription factor binding to RING finger protein 10

  • Jijin Lin
  • Mona T. Friesen
  • Patricia Bocangel
  • David Cheung
  • Kathy Rawszer
  • Jeffrey T. Wigle
Article

Abstract

The molecular mechanisms by which Mesenchyme Homeobox 2 (Meox2) regulates the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes are not known. The discovery of MEOX2 binding proteins will aid in understanding how MEOX2 functions as a regulator of these key cellular processes. To identify MEOX2 binding proteins, a yeast two-hybrid screen of a human heart cDNA library was performed using a deleted MEOX2 bait protein that does not contain the histidine/glutamine rich region (MEOX2ΔHQ). Eleven putative interacting proteins were identified including RING finger protein 10 (RNF10). In vitro pull-down assays and co-immunoprecipitation studies in mammalian cells further supported the yeast data demonstrating RNF10 bound to MEOX2. The minimal RNF10 binding region of MEOX2 was determined to be a central region between the histidine/glutamine rich domain and the homeodomain (amino acids 101–185). The amino terminal region of RNF10, containing the RING finger domain, was not essential for the binding to MEOX2. Our results also demonstrated that MEOX2 activation of the p21WAF1 promoter was enhanced by RNF10 co-expression.

Keywords

MEOX Meox denotes gene MEOX denotes protein protein–protein interaction RING finger protein transcription factor yeast two-hybrid 

References

  1. 1.
    Ross R: Cell biology of atherosclerosis. Annu Rev Physiol 57: 791–804, 1995Google Scholar
  2. 2.
    Sriram V, Patterson C: Cell cycle in vasculoproliferative diseases: potential interventions and routes of delivery. Circulation 103: 2414–2419, 2001Google Scholar
  3. 3.
    Zettler ME, Pierce GN: Cell cycle proteins and atherosclerosis. Herz 25: 100–107, 2000Google Scholar
  4. 4.
    Berk BC: Vascular smooth muscle growth: autocrine growth mechanisms. Physiol Rev 81: 999–1030, 2001Google Scholar
  5. 5.
    Casscells W: Migration of smooth muscle and endothelial cells. Critical events in restenosis. Circulation 86: 723–729, 1992Google Scholar
  6. 6.
    Gibbons GH, Dzau VJ: The emerging concept of vascular remodeling. New Engl J Med 330: 1431–1438, 1994Google Scholar
  7. 7.
    Orlic D: Adult bone marrow stem cells regenerate myocardium in ischemic heart disease. Ann N Y Acad Sci 996: 152–157, 2003Google Scholar
  8. 8.
    Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P: Bone marrow stem cells regenerate infarcted myocardium. Pediatr Transplant 7(suppl 3): 86–88, 2003Google Scholar
  9. 9.
    Zhang Y, Griffith EC, Sage J, Jacks T, Liu JO: Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21WAF1/CIP1. Proc Natl Acad Sci USA 97: 6427–6432, 2000Google Scholar
  10. 10.
    Kibbe MR, Billiar TR, Tzeng E: Gene therapy for restenosis. Circ Res 86: 829–833, 2000Google Scholar
  11. 11.
    Braun-Dullaeus RC, Mann MJ, Dzau VJ: Cell cycle progression: New therapeutic target for vascular proliferative disease. Circulation 98: 82–89, 1998Google Scholar
  12. 12.
    Li RK, Yau TM, Sakai T, Mickle DA, Weisel RD: Cell therapy to repair broken hearts. Can J Cardiol 14: 735–744, 1998Google Scholar
  13. 13.
    Gehring WJ, Affolter M, Burglin T: Homeodomain proteins. Annu Rev Biochem 63: 487–526, 1994Google Scholar
  14. 14.
    Gorski DH, LePage DF, Patel CV, Copeland NG, Jenkins NA, Walsh K: Molecular cloning of a diverged homeobox gene that is rapidly down-regulated during the G0/G1 transition in vascular smooth muscle cells. Mol Cell Biol 13: 3722–3733, 1993Google Scholar
  15. 15.
    Gorski DH, Leal AJ: Inhibition of endothelial cell activation by the homeobox gene Gax. J Surg Res 111: 91–99, 2003Google Scholar
  16. 16.
    Watanabe D, Takagi H, Suzuma K, Suzuma I, Oh H, Ohashi H, Kemmochi S, Uemura A, Ojima T, Suganami E, Miyamoto N, Sato Y, Honda Y: Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization. Am J Pathol 164: 1827–1835, 2004Google Scholar
  17. 17.
    Mano T, Luo Z, Malendowicz SL, Evans T, Walsh K: Reversal of GATA-6 downregulation promotes smooth muscle differentiation and inhibits intimal hyperplasia in balloon-injured rat carotid artery. Circ Res 84: 647–654, 1999Google Scholar
  18. 18.
    Fisher SA, Siwik E, Branellec D, Walsh K, Watanabe MM: Forced expression of the homeodomain protein Gax inhibits cardiomyocyte proliferation and perturbs heart morphogenesis. Development 124: 4405–4413, 1997Google Scholar
  19. 19.
    Smith RC, Branellec D, Gorski DH, Guo K, Perlman H, Dedieu JF, Pastore C, Mahfoudi A, Denefle P, Isner JM, Walsh KM: p21CIP1-mediated inhibition of cell proliferation by overexpression of the gax homeodomain gene. Genes Dev 11: 1674–1689, 1997Google Scholar
  20. 20.
    Perlman H, Luo Z, Krasinski K, Le Roux A, Mahfoudi A, Smith RC, Branellec D, Walsh KM: Adenovirus-mediated delivery of the Gax transcription factor to rat carotid arteries inhibits smooth muscle proliferation and induces apoptosis. Gene Ther 6: 758–763, 1999Google Scholar
  21. 21.
    Maillard L, Van Belle E, Smith RC, Le Roux A, Denefle P, Steg G, Barry JJ, Branellec D, Isner JM, Walsh KM: Percutaneous delivery of the gax gene inhibits vessel stenosis in a rabbit model of balloon angioplasty. Cardiovasc Res 35: 536–546, 1997Google Scholar
  22. 22.
    Candia AF, Hu J, Crosby J, Lalley PA, Noden D, Nadeau JH, Wright CV: Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 116: 1123–1136, 1992Google Scholar
  23. 23.
    Stamataki D, Kastrinaki M, Mankoo BS, Pachnis V, Karagogeos DM: Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors. FEBS Lett 499: 274–278, 2001Google Scholar
  24. 24.
    Mankoo BS, Skuntz S, Harrigan I, Grigorieva E, Candia A, Wright CV, Arnheiter H, Pachnis V: The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites. Development 130: 4655–4664, 2003Google Scholar
  25. 25.
    Seki N, Hattori A, Sugano S, Muramatsu M, Saito T: cDNA cloning, expression profile, and genomic structure of human and mouse RNF10/Rnf 10 genes, encoding a novel RING finger protein. J Hum Genet 45: 38–42, 2000Google Scholar
  26. 26.
    Gorski DH, Leal AJM: Inhibition of endothelial cell activation by the homeobox gene Gax. J Surg Res 111: 91–99, 2003Google Scholar
  27. 27.
    Seki N, Hattori A, Sugano S, Suzuki Y, Nakagawara A, Ohhira M, Muramatsu M, Hori T, Saito T: Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif. J Hum Genet 43: 272–274, 1998Google Scholar
  28. 28.
    Ueki N, Seki N, Yano K, Masuho Y, Saito T, Muramatsu M: Isolation and characterization of a novel human gene (HFB30) which encodes a protein with a RING finger motif. Biochim Biophys Acta 1445: 232–236, 1999Google Scholar
  29. 29.
    Mercader N, Leonardo E, Azpiazu N, Serrano A, Morata G, Martinez C, Torres M: Conserved regulation of proximodistal limb axis development by Meis1/Hth. Nature 402: 425–429, 1999Google Scholar
  30. 30.
    Qu L, Huang S, Baltzis D, Rivas-Estilla AM, Pluquet O, Hatzoglou M, Koumenis C, Taya Y, Yoshimura A, Koromilas AE: Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta. Genes Dev 18: 261–277, 2004Google Scholar
  31. 31.
    Kwek SS, Derry J, Tyner AL, Shen Z, Gudkov AV: Functional analysis and intracellular localization of p53 modified by SUMO-1. Oncogene 20: 2587–2599, 2001Google Scholar
  32. 32.
    Boyd SD, Tsai KY, Jacks T: An intact HDM2 RING-finger domain is required for nuclear exclusion of p53. Nat Cell Biol 2: 563–568, 2000Google Scholar
  33. 33.
    Saurin AJ, Borden KL, Boddy MN, Freemont PS: Does this have a familiar RING? Trends Biochem Sci 21: 208–214, 1996Google Scholar
  34. 34.
    Borden KL, Boddy MN, Lally J, O’Reilly NJ, Martin S, Howe K, Solomon E, Freemont PS: The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. Embo J 14: 1532–1541, 1995Google Scholar
  35. 35.
    Borden KL, Freemont PS: The RING finger domain: A recent example of a sequence-structure family. Curr Opin Struct Biol 6: 395–3401, 1996Google Scholar
  36. 36.
    Borden KL, Campbell Dwyer EJ, Salvato MS: The promyelocytic leukemia protein PML has a pro-apoptotic activity mediated through its RING domain. FEBS Lett 418: 30–34, 1997Google Scholar
  37. 37.
    Barlow PN, Luisi B, Milner A, Elliott M, Everett R: Structure of the C3HC4 domain by 1H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger. J Mol Biol 237: 201–211, 1994Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Jijin Lin
    • 1
    • 2
    • 4
  • Mona T. Friesen
    • 1
    • 2
  • Patricia Bocangel
    • 1
    • 2
  • David Cheung
    • 1
    • 2
  • Kathy Rawszer
    • 2
    • 3
  • Jeffrey T. Wigle
    • 1
    • 2
    • 5
  1. 1.Department of Biochemistry and Medical GeneticsUniversity of ManitobaWinnipeg
  2. 2.Division of Stroke and Vascular DiseaseSt. Boniface General Hospital Research CentreWinnipeg
  3. 3.Department of BiologyUniversity of WinnipegWinnipeg
  4. 4.The First Affiliated Hospital of Shantou University Medical CollegeShantouChina
  5. 5.Division of Stroke and Vascular DiseaseSt. Boniface General Hospital Research CentreWinnipeg

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