Skip to main content
SpringerLink
Log in

High-mobility-group proteins and cancer—an emerging link

  • Guest Editorial
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

In the last few years, considerable interest has been generated in the role of high-mobility-group (HMG) proteins, and HMG box proteins generally, in cancer development and therapy. These proteins were discovered in the early 1970s (Goodwin et al. 1973) as a group of nonhistone proteins. Some members of the HMG protein family (i) constitute a class of important architectural proteins involved in transcriptional regulation of genes, (ii) are frequently expressed in transformed cells at levels that correlate with the degree of neoplastic cell transformation, (iii) participate in gene rearrangements, which are linked to the emergence of benign solid tumors, (iv) confer the ability to recognize DNA-cisplatin adducts selectively, and (v) provide a new delivery system for efficient gene transfer. It should be considered that some HMG proteins, acting as architectural proteins that bring many of the transcription factors into precise three-dimensional shapes, may have a similar critical role in neoplastic-transformation to that of some transcription factors themselves.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Aizawa S, Nishino H, Saito K, Kimura K, Shirakawa H, Yoshida M (1994) Stimulation of transcription in cultured cells by high mobility group protein 1: essential role of the acidic carboxylterminal region. Biochemistry 33: 14690–14695

    Google Scholar 

  • Arnold W, Böttger M, Hauff P, Rudolph M, Scherneck S (1992) Neoplastic changes in HPV 11 and HPV 11 DNA/HMG1 complex-infected human foreskin tissues using subrenal capsule technique in nude andscid mice. Contrib Oncol 42: 294–302

    Google Scholar 

  • Ashar HR, Schoenberg Fejzo M, Tkachenko A, Zhou X, Fletcher JA, Weremowicz S, Morton CC, Chada K (1995) Disruption of the architectural factor HMGI-C: DNA binding AT motifs fused in lipomas to distinct transcriptional regulatory domains. Cell 82: 57–65

    Google Scholar 

  • Ashar HR, Cherath L, Przybysz KM, Chada K (1996) Genomic characterization for human HMGIC, a member of the accessory transcription factor family found at translocation breakpoints in lipomas. Genomics 31: 207–214

    Google Scholar 

  • Baxevanis AD, Landsman D (1995) The HMG box protein family: classification and functional relationships. Nucleic Acids Res 23:1604–1613

    Google Scholar 

  • Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W (1996) Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382: 638–642

    Google Scholar 

  • Bellon SF, Coleman JH, Lippard SJ (1991) DNA unwinding produced by site-specific intrastrand cross-links of the antitumor drugcis-diamminedichloroplatinum (II). Biochemistry 30: 8026–8035

    Google Scholar 

  • Berlingieri MT, Manfioletti G, Santoro M, Bandiera A, Visconti R, Giancotti V, Fusco A (1995) Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells. Mol Cell Biol 15: 1545–1553

    Google Scholar 

  • Bianchi ME (1991) Production of functional rat HMG1 protein inEscherichia coli. Gene 104: 271–275

    Google Scholar 

  • Böttger M, Vogel F, Platzer M, Kiessling U, Grade K, Strauss M (1988) Condensation of vector DNA by the chromosomal protein HMG1 results in efficient transfection. Biochim Biophys Acta 950: 221–228

    Google Scholar 

  • Böttger M, Platzer M, Kiessling U, Strauss M (1990) Transfection by DNA-nuclear protein HMG1 complexes: raising of efficiency and role of DNA topology. Arch Geschwulstforsch 60: 265–270

    Google Scholar 

  • Böttger M, Arnold W, Zaitsev S, Vorob'ev VI, Haberland A, Schimke I (1996) HMG1-effected gene transfer using cell cultures and tissue explants xenografted in immunodeficient mice. Contrib Oncol 51: 36–40

    Google Scholar 

  • Brown SJ, Kellett PJ, Lippard SJ (1993) Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin. Science 261: 603–605

    Google Scholar 

  • Bruhn SL, Pil PM, Essigmann JM, Housman DE, Lippard SJ (1992) Isolation and characterization of human cDNA clones encoding a high mobility group box protein that recognizes structural distortions to DNA caused by binding of the anticancer agent cisplatin. Proc Natl Acad Sci USA 89: 2307–2311

    Google Scholar 

  • Bussemakers MJG, WJM van de Ven, Debruyne FMJ, Schalken SA (1991) Identification of high mobility group protein I(Y) as potential progression marker for prostate cancer by differential hybridization analysis. Cancer Res 51: 606–611

    Google Scholar 

  • Bustin M, Lehn DA, Landsman D (1990) Structural features of the HMG chromosomal proteins and their genes. Biochim Biophys Acta 1049: 231–243

    Google Scholar 

  • Bustin M, Trieschmann L, Postnikov YV (1995) The HMG-14/-17 chromosomal protein family: architectural elements that enhance transcription from chromatin templates. Semin Cell Biol 6: 247–255

    Google Scholar 

  • Chau K-Y, Patel UA, Lee K-LD, Lam H-YP, Crane-Robinson C (1995) The gene for the human architectural transcription factor HMGI-C consists of five exons each coding for a distinct functional element. Nucleic Acids Res 23: 4262–4266

    Google Scholar 

  • Chiappetta G, Bandiera A, Berlingieri MT, Visconti R, Manfioletti G, Battista S, Martinez-Tello FJ, Santoro M, Giancotti V, Fusco A (1995) The expression of the high mobility group HMGI(Y) proteins correlates with the malignant phenotype of human thyroid neoplasias. Oncogene 10: 1307–1314

    Google Scholar 

  • Cleaver JE, Hultner ML (1995) Transcription-related human disorders. Am J Hum Genet 56: 1257–1261

    Google Scholar 

  • Dzau VJ, Morishita R, Gibbons GH (1993) Gene therapy for cardiovascular disease. Trends Biotechnol 11: 205–210

    Google Scholar 

  • Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, Casamassimi A, Santoro M, Giancotti V, Fusco A (1996) Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins. Cancer Res 56: 1896–1901

    Google Scholar 

  • Gaillard C, Strauss F (1994) Association of poly (CA)·poly (TG) DNA fragments into four-stranded complexes bound by HMG 1 and 2. Science 264: 433–436

    Google Scholar 

  • Giancotti V, Berlingieri MT, Di Fiore PP, Fusco A, Vecchio G, Crane-Robinson C (1985) Changes in nuclear proteins on transformation of rat epithelial thyroid cells by a murine sarcoma retrovirus. Cancer Res 45: 6051–6057

    Google Scholar 

  • Giancotti V, Pani B, D'Andrea P, Berlingieri MT, Di Fiore PP, Fusco A, Vecchio G, Philp R, Crane-Robinson C, Nicolas RH, Wright CA, Goodwin GH (1987) Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by co-transfection with c-myc and polyoma middle T genes. EMBO J 6: 1981–1987

    Google Scholar 

  • Giancotti V, Buratti E, Perissin L, Zorzet S, Balmain A, Portella G, Fusco A, Goodwin GH (1989) Analysis of the HMGI nuclear proteins in mouse neoplastic cells induced by different procedures. Exp Cell Res 184: 538–545

    Google Scholar 

  • Giancotti V, Bandiera A, Ciani L, Santoro D, Crane-Robinson C, Goodwin GH, Boiocchi M, Dolcetti R, Casetta B (1993) Highmobility-group (HMG) proteins and histone H1 subtypes expression in normal and tumor tissues of mouse. Eur J Biochem 213: 825–832

    Google Scholar 

  • Giese K, Cox J, Grosschedl R (1992) The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69: 185–195

    Google Scholar 

  • Goodwin GH, Sanders C, Johns EW (1973) A new group of chromatinassociated proteins with a high content of acidic and basic amino acids. Eur J Biochem 38: 14–19

    Google Scholar 

  • Grossbach U (1995) Selective distribution of histone H1 variants and high mobility group proteins in chromosomes. Semin Cell Biol 6: 237–246

    Google Scholar 

  • Grosschedl R, Giese K, Pagel J (1994) HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet 10: 94–100

    Google Scholar 

  • Henderson D, Hurley LH (1995) Molecular struggle for transcriptional control. Nat Med 1: 525–527

    Google Scholar 

  • Hesketh R (1995) The oncogene facts book. Academic Press, London San Diego New York

    Google Scholar 

  • Hughes EN, Engelsberg BN, Billings PC (1992) Purification of nuclear proteins that bind to cisplatin-damaged DNA. Identity with high mobility group proteins 1 and 2. J Biol Chem 267: 13520–13527

    Google Scholar 

  • Jantzen H-M, Admon A, Bell SP, Tjian R (1990) Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. Nature 344: 830–836

    Google Scholar 

  • John S, Reeves RB, Lin J-X, Child R, Leiden JM, Thompson CB, Leonard WJ (1995) Regulation of cell-type-specific interleukin-2 receptor α-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kB family proteins. Mol Cell Biol 15: 1786–1796

    Google Scholar 

  • Johns EW (ed) (1982) The HMG chromosomal proteins. Academic Press, Orlando, Fla

    Google Scholar 

  • Kaneda Y, Iwai K, Uchida T (1989) Increased expression of DNA conintroduced with nuclear protein in adult rat liver. Science 243: 375–378

    Google Scholar 

  • Kato K, Nakanishi M, Kaneda Y, Uchida T, Okada Y (1991) Expression of hepatitis B virus surface antigen in adult liver: co-introduction of DNA and nuclear protein by a simplified liposome method. J Biol Chem 266: 3361–3364

    Google Scholar 

  • Kazmierczak B, Hennig Y, Wanschura S, Rogalla P, Bartnitzke S, Van de Ven W, Bullerdiek J (1995) Description of a novel fusion transcript between HMGI-C, a gene encoding for a member of the high mobility group proteins, and the mitochondrial aldehyde dehydrogenase gene. Cancer Res 55: 6038–6039

    Google Scholar 

  • Kazmierczak B, Rosigkeit J, Wanschura S, Meyer-Bolte K, Van de Ven W, Kayser K, Krieghoff B, Kastendiek H, Bartnitzke S, Bullerdiek J (1996) HMGI-C rearrangements as the molecular basis for the majority of pulmonary chondroid hamartomas: a survey of 30 tumors. Oncogene 12: 515–521

    Google Scholar 

  • Leger H, Sock E, Renner K, Grummt F, Wegner M (1995) Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y. Mol Cell Biol 15: 3738–3747

    Google Scholar 

  • Lehming N, Thanos D, Brickman JM, Ma J, Maniatis T, Ptashne M (1994) An HMG-like protein that can switch a transcriptional activator to a repressor. Nature 371: 175–179

    Google Scholar 

  • Lewis H, Kaszubska W, DeLamarter JF, Whelan J (1994) Cooperativity between two NF-kB complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter. Mol Cell Biol 14: 5701–5709

    Google Scholar 

  • Love JJ, Li X, Case DA, Giese K, Grosschedl R, Wright PE (1995) Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376: 791–795

    Google Scholar 

  • Lund T, Holtlund J, Fredriksen M, Laland SG (1983) On the presence of two new high mobility group-like proteins in HeLa S3 Cells. FEBS Lett 152: 163–167

    Google Scholar 

  • MacLeod MC, Powell KL, Tran N (1995) Binding of the transcription factor, SP1, to non-target sites in DNA modified by benzo[a]pyrene diol epoxide. Carcinogenesis 16: 975–983

    Google Scholar 

  • Manfioletti G, Giancotti V, Bandiera A, Buratti E, Sautière P, Cary P, Crane-Robinson C, Coles B, Goodwin GH (1991) cDNA cloning of the HMGI-C phosphoprotein, a nuclear protein associated with neoplastic and undifferentiated phenotypes. Nucleic Acids Res 19: 6793–6797

    Google Scholar 

  • McA'Nulty MM, Lippard SJ (1996) The HMG-domain protein Ixr1 blocks excision repair of cisplatin-DNA adducts in yeast. Mutat Res 362: 75–86

    Google Scholar 

  • Ner SS, Travers AA, Churchill MEA (1994) Harnessing the writhe: a role for DNA chaperones in nucleoprotein-complex formation. Trends Biochem Sci 19: 185–187

    Google Scholar 

  • Ogram SA, Reeves R (1995) Differential regulation of a multipromoter gene. Selective 12-O-tetradecanoylphorbol-13-acetate induction of a single transcription start site in theHMGI/Y gene. J Biol Chem 270: 14235–14242

    Google Scholar 

  • Patel UA, Bandiera A, Manfioletti G, Giancotti V, Chau K-Y, Crane-Robinson C (1994) Expression and cDNA cloning of human HMGI-C phosphoprotein. Biochem Biophys Res Commun 201: 63–70

    Google Scholar 

  • Rabbitts TH (1994) Chromosomal translocations in human cancer. Nature 372: 143–149

    Google Scholar 

  • Ram TG, Reeves R, Hosick HL (1993) Elevated high mobility group I(Y) gene expression is associated with progressive transformation of mouse mammary epithelial cells. Cancer Res 53: 2655–2660

    Google Scholar 

  • Read CM, Cary PD, Crane-Robinson S, Driscoll PC, Carrillo MOM, Norman DG (1995) The structure of the HMG box and its interaction with DNA. In: Eckstein F, Lilley DMJ (eds) Nucleic acids and molecular biology 9: 222–250

  • Sandig V, Stamm W, Behlke J, Böttger M, Strauss M (1995) Direct gene transfer of HMG1 based DNA-protein complexes (abstract). J Mol Med 73: B10

    Google Scholar 

  • Schoenmakers EFPM, Wanschura S, Mols R, Bullerdiek J, Van den Berghe H, Van de Ven WJM (1995) Recurrent rearrangements in the high mobility group protein gene,HMGI-C in benign mesenchymal tumours. Nat Genet 10: 436–444

    Google Scholar 

  • Sheridan PL, Sheline CT, Cannon K, Voz ML, Pazin MJ, Kadonaga JT, Jones KA (1995) Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro. Genes Dev 9: 2090–2104

    Google Scholar 

  • Shirakata M, Hüppi K, Usuda S, Okazaki K, Yoshida K, Sakano H (1991) HMG1-related DNA-binding protein isolated with V-(D)-J recombination signal probes. Mol Cell Biol 11: 4528–4536

    Google Scholar 

  • Takahara PM, Rosenzweig MC, Frederick CA Lippard SJ (1995) Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin. Nature 377: 649–652

    Google Scholar 

  • Thanos D, Maniatis T (1992) The high mobility group protein HMGI(Y) is required for NFkB-dependent virus induction of the human IFNβ gene. Cell 71: 777–789

    Google Scholar 

  • Thanos D, Maniatis T (1995) Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome. Cell 83: 1091–1100

    Google Scholar 

  • Tmimi Y, van der Poel HG, Denyn MM, Umbas R, Karthaus HFM, Debruyne FMJ, Shalken JA (1993) Increased expression of high mobility group protein I(Y) in high grade prostate cancer determined by in situ hybridization. Cancer Res 53: 5512–5516

    Google Scholar 

  • Treiber DK, Zhai X, Jantzen H-M, Essigmann JM (1994) Cisplatin-DNA adducts are molecular decoys for the ribosomal RNA transcription factor hUBF (human upstream binding factor). Proc Natl Acad Sci USA 91: 5672–5676

    Google Scholar 

  • Tricoli JV, Yao JL, D'Souza SA, Bracken RB (1993) Detection of sex-region Y (SRY) transcripts in human prostate adenocarcinoma and benign prostatic hypertrophy. Genes Chromosomes Cancer 8: 28–33

    Google Scholar 

  • Verbeek S, Izon D, Hofhuis F, Robanus-Maandag E, de Riele H, van de Wetering M, Oosterwegel M, Wilson A, Robson MacDonald H, Clevers H (1995) An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374: 70–74

    Google Scholar 

  • Wagner JP, Quill DM, Pettijohn DE (1995) Increased DNA-bending activity and higher affinity DNA binding of high mobility group protein HMG-1 prepared without acids. J Biol Chem 270: 7394–7398

    Google Scholar 

  • Wanschura S, Schoenmakers EFPM, Huysmans C, Bartnizke S, Van de Ven WJM, Bullerdiek J (1996) Mapping of the gene encoding the human hepatoma-derived growth factor (HDGF) with homology to the high-mobility group (HMG)-1 protein to Xq25. Genomics 32: 298–300

    Google Scholar 

  • Watanabe F, Shirakawa H, Yoshida M, Tsukada K, Teraoka H (1994) Stimulation of DNA-dependent protein kinase activity by high mobility group proteins 1 and 2. Biochem Biophys Res Commun 202: 736–742

    Google Scholar 

  • Werner MH, Gronenborn AM, Clore GM (1996) Intercalation, DNA kinking, and the control of transcription. Science 271: 778–784

    Google Scholar 

  • Wood LD, Farmer AA, Richmond A (1995) HMGI(Y) and Sp1 in addition to NF-kB regulate transcription of the MGSA/GROα gene. Nucleic Acids Res 23: 4210–4219

    Google Scholar 

  • Yamazaki F, Nagatsuka Y, Shirakawa H, Yoshida M (1995) Repression of cell cycle progression by antisense HMG2 RNA. Biochem Biophys Res Commun 210: 1045–1051

    Google Scholar 

  • Zamble DB, Lippard SJ (1995) Cisplatin and DNA repair in cancer chemotherapy. Trends Biochem Sci 20: 435–439

    Google Scholar 

  • Zhou X, Benson KF, Ashar HR, Chada K (1995) Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature 376: 771–774

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biology, Humboldt-University Berlin, c/o Max-Delbrück-Center for Molecular Medicine, Robert-Rösslestr. 10, 13125, Berlin, Germany

    Volker Wunderlich

  2. Department of Cardiology, 1st Medical Clinic, Charité, Humboldt University Berlin, c/o Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany

    Michael Böttger

Authors
  1. Volker Wunderlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Böttger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Volker Wunderlich.

Additional information

Dedicated to Professor Erich Hecker on the occasion of his 70th birthday

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wunderlich, V., Böttger, M. High-mobility-group proteins and cancer—an emerging link. J Cancer Res Clin Oncol 123, 133–140 (1997). https://doi.org/10.1007/BF01214665

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01214665

Key words

Search

Navigation