HMGB1 and HMGB2 proteins up-regulate cellular expression of human topoisomerase IIα

Topoisomerase IIα (topo IIα) is a nuclear enzyme involved in several critical processes, including chromosome replication, segregation and recombination. Previously we have shown that chromosomal protein HMGB1 interacts with topo IIα, and stimulates its catalytic activity. Here we show the effect of HMGB1 on the activity of the human topo IIα gene promoter in different cell lines. We demonstrate that HMGB1, but not a mutant of HMGB1 incapable of DNA bending, up-regulates the activity of the topo IIα promoter in human cells that lack functional retinoblastoma protein pRb. Transient over-expression of pRb in pRb-negative Saos-2 cells inhibits the ability of HMGB1 to activate the topo IIα promoter. The involvement of HMGB1 and its close relative, HMGB2, in modulation of activity of the topo IIα gene is further supported by knock-down of HMGB1/2, as evidenced by significantly decreased levels of topo IIα mRNA and protein. Our experiments suggest a mechanism of up-regulation of cellular expression of topo IIα by HMGB1/2 in pRb-negative cells by modulation of binding of transcription factor NF-Y to the topo IIα promoter, and the results are discussed in the framework of previously observed pRb-inactivation, and increased levels of HMGB1/2 and topo IIα in tumors.

[1]  T. Karn,et al.  Gene expression of topoisomerase II alpha (TOP2A) by microarray analysis is highly prognostic in estrogen receptor (ER) positive breast cancer , 2009, Breast Cancer Research and Treatment.

[2]  D. Edwards,et al.  Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding , 2008, Nucleic acids research.

[3]  F. O'Malley,et al.  HER-2 and topoisomerase II as predictors of response to chemotherapy. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  M. Miyazaki,et al.  Upregulation of topoisomerase IIα expression in advanced gallbladder carcinoma: a potential chemotherapeutic target , 2008, Journal of Cancer Research and Clinical Oncology.

[5]  Matthew A. Watson,et al.  Mapping intramolecular interactions between domains in HMGB1 using a tail-truncation approach. , 2007, Journal of molecular biology.

[6]  S. Fan,et al.  Growth suppression and radiosensitivity increase by HMGB1 in breast cancer , 2007, Acta Pharmacologica Sinica.

[7]  P. Garred,et al.  The genetic variation of the human HMGB1 gene. , 2007, Tissue antigens.

[8]  J. Štokrová,et al.  HMGB1 interacts with human topoisomerase IIα and stimulates its catalytic activity , 2007, Nucleic acids research.

[9]  K. Grasser,et al.  The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins , 2007, Cellular and Molecular Life Sciences.

[10]  Robin L. Jones,et al.  Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer , 2007, Breast Cancer Research and Treatment.

[11]  D. Goodrich,et al.  The retinoblastoma tumor suppressor protein is required for efficient processing and repair of trapped topoisomerase II-DNA-cleavable complexes , 2005, Oncogene.

[12]  Christian D Muller,et al.  The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle , 2005, Oncogene.

[13]  M. Štros,et al.  Determinants of specific binding of HMGB1 protein to hemicatenated DNA loops. , 2005, Journal of molecular biology.

[14]  M. Bianchi,et al.  HMG proteins: dynamic players in gene regulation and differentiation. , 2005, Current opinion in genetics & development.

[15]  S. Joos,et al.  Increased expression of high mobility group box 1 (HMGB1) is associated with an elevated level of the antiapoptotic c-IAP2 protein in human colon carcinomas , 2005, Gut.

[16]  N. Osheroff,et al.  Etoposide, topoisomerase II and cancer. , 2005, Current medicinal chemistry. Anti-cancer agents.

[17]  Pearlly Yan,et al.  Chromatin Immunoprecipitation (ChIP) on Chip Experiments Uncover a Widespread Distribution of NF-Y Binding CCAAT Sites Outside of Core Promoters* , 2005, Journal of Biological Chemistry.

[18]  M. Hande,et al.  Yeast Nhp6A/B and Mammalian Hmgb1 Facilitate the Maintenance of Genome Stability , 2005, Current Biology.

[19]  H. Shirakawa,et al.  Acidic C-tail of HMGB1 is required for its target binding to nucleosome linker DNA and transcription stimulation. , 2004, Biochemistry.

[20]  M. Bianchi.  Significant (re)location: how to use chromatin and/or abundant proteins as messages of life and death. , 2004, Trends in cell biology.

[21]  W. Denny.  Emerging DNA topoisomerase inhibitors as anticancer drugs , 2004 .

[22]  B. Spike,et al.  New roles for the RB tumor suppressor protein. , 2004, Current opinion in genetics & development.

[23]  S. Fesik,et al.  siRNA-mediated gene silencing: a global genome view. , 2004, Nucleic acids research.

[24]  E. Liu,et al.  Topoisomerase IIα gene (TOP2A) amplification and deletion in cancer – more common than anticipated , 2003, Cytopathology : official journal of the British Society for Clinical Cytology.

[25]  R. Isaacs,et al.  Modulation of DNA topoisomerase II alpha promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors. , 2003, The Biochemical journal.

[26]  Stefan Joos,et al.  HMGB1 inhibits cell death in yeast and mammalian cells and is abundantly expressed in human breast carcinoma , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  T. Kundu,et al.  The acidic C-terminal domain and A-box of HMGB-1 regulates p53-mediated transcription. , 2003, Nucleic acids research.

[28]  F. Murphy,et al.  The role of intercalating residues in chromosomal high-mobility-group protein DNA binding, bending and specificity. , 2003, Nucleic acids research.

[29]  M. Bianchi,et al.  HMGB proteins and gene expression. , 2003, Current opinion in genetics & development.

[30]  M. Gaub,et al.  Modification of topoisomerase genes copy number in newly diagnosed childhood acute lymphoblastic leukemia , 2003, Leukemia.

[31]  S. Lippard,et al.  Nature of full-length HMGB1 binding to cisplatin-modified DNA. , 2003, Biochemistry.

[32]  C. Lok,et al.  Characterization of the human topoisomerase IIbeta (TOP2B) promoter activity: essential roles of the nuclear factor-Y (NF-Y)- and specificity protein-1 (Sp1)-binding sites. , 2002, The Biochemical journal.

[33]  C. Bronner,et al.  Overexpression of ICBP90, a novel CCAAT-binding protein, overcomes cell contact inhibition by forcing topoisomerase II alpha expression. , 2002, Anticancer research.

[34]  JAMES C. Wang,et al.  Cellular roles of DNA topoisomerases: a molecular perspective , 2002, Nature Reviews Molecular Cell Biology.

[35]  A. Yamauchi,et al.  Topoisomerase IIα gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients , 2002, Cancer.

[36]  J. Feigon,et al.  Binding to cisplatin-modified DNA by the Saccharomyces cerevisiae HMGB protein Nhp6A. , 2002, Biochemistry.

[37]  J. Bernués,et al.  HMGB1 Interacts with Many Apparently Unrelated Proteins by Recognizing Short Amino Acid Sequences* , 2002, The Journal of Biological Chemistry.

[38]  A. Nakagawara,et al.  HMGB1 and HMGB2 Cell-specifically Down-regulate the p53- and p73-dependent Sequence-specific Transactivation from the Human Bax Gene Promoter* , 2002, The Journal of Biological Chemistry.

[39]  C. Bronner,et al.  Transcriptional regulation of the human topoisomerase IIalpha gene. , 2002, Anticancer research.

[40]  Y. Mo,et al.  Cytotoxic signalling by inhibitors of DNA topoisomerase II. , 2001, Biochemical Society transactions.

[41]  W. Scovell,et al.  The Binding Interaction of HMG-1 with the TATA-binding Protein/TATA Complex* , 2001, The Journal of Biological Chemistry.

[42]  H. Schöler,et al.  Reduced fertility and spermatogenesis defects in mice lacking chromosomal protein Hmgb2. , 2001, Development.

[43]  M. Štros.  Two mutations of basic residues within the N-terminus of HMG-1 B domain with different effects on DNA supercoiling and binding to bent DNA. , 2001, Biochemistry.

[44]  A. Travers,et al.  HMG1 and 2, and related 'architectural' DNA-binding proteins. , 2001, Trends in biochemical sciences.

[45]  W. T. Beck,et al.  Role of an inverted CCAAT element in human topoisomerase IIalpha gene expression in ICRF-187-sensitive and -resistant CEM leukemic cells. , 2001, Molecular pharmacology.

[46]  A Benner,et al.  Genomic aberrations and survival in chronic lymphocytic leukemia. , 2000, The New England journal of medicine.

[47]  S. Lippard,et al.  Intercalating residues determine the mode of HMG1 domains A and B binding to cisplatin-modified DNA. , 2000, Biochemistry.

[48]  P. Guida,et al.  pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at physiologically relevant levels , 2000, Oncogene.

[49]  Y. Kwon,et al.  The p53 Tumor Suppressor Stimulates the Catalytic Activity of Human Topoisomerase IIα by Enhancing the Rate of ATP Hydrolysis* , 2000, The Journal of Biological Chemistry.

[50]  S. Lippard,et al.  Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[51]  R. Seong,et al.  Sp1 mediates cell proliferation-dependent regulation of rat DNA topoisomerase IIalpha gene promoter. , 1999, The Biochemical journal.

[52]  R. Mantovani,et al.  The molecular biology of the CCAAT-binding factor NF-Y. , 1999, Gene.

[53]  W. T. Beck,et al.  Functional interaction between human topoisomerase IIalpha and retinoblastoma protein. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[54]  A. Aguzzi,et al.  The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice , 1999, Nature Genetics.

[55]  R. Broadhurst,et al.  DNA-binding properties of the tandem HMG boxes of high-mobility-group protein 1 (HMG1). , 1998, European journal of biochemistry.

[56]  M. Štros,et al.  DNA bending by the chromosomal protein HMG1 and its high mobility group box domains. Effect of flanking sequences. , 1998, The Journal of biological chemistry.

[57]  C. Prives,et al.  High mobility group protein-1 (HMG-1) is a unique activator of p53. , 1998, Genes & development.

[58]  L. Zwelling,et al.  Evaluation of a potential regulatory role for inverted CCAAT boxes in the human topoisomerase II alpha promoter. , 1997, Biochemical and biophysical research communications.

[59]  G. Zambetti,et al.  Inhibition of DNA topoisomerase II alpha gene expression by the p53 tumor suppressor , 1997, Molecular and cellular biology.

[60]  A. Harris,et al.  p53 Regulates the Minimal Promoter of the Human Topoisomerase IIα Gene , 1996 .

[61]  M. Rocchi,et al.  The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13. , 1996, Genomics.

[62]  A. Harris,et al.  Regulation of the Human Topoisomerase IIα Gene Promoter in Confluence-arrested Cells* , 1996, The Journal of Biological Chemistry.

[63]  J. O. Thomas,et al.  Differences in the DNA-binding properties of the HMG-box domains of HMG1 and the sex-determining factor SRY. , 1995, European journal of biochemistry.

[64]  R. Weinberg,et al.  The retinoblastoma protein and cell cycle control , 1995, Cell.

[65]  M. Yoshida,et al.  Stimulation of transcription in cultured cells by high mobility group protein 1: essential role of the acidic carboxyl-terminal region. , 1994, Biochemistry.

[66]  J. Štokrová,et al.  DNA looping by the HMG-box domains of HMG1 and modulation of DNA binding by the acidic C-terminal domain. , 1994, Nucleic acids research.

[67]  S. Lippard,et al.  High-mobility-group 1 protein mediates DNA bending as determined by ring closures. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[68]  R. C. Johnson,et al.  The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. , 1993, Genes & development.

[69]  L. Sheflin,et al.  The specific interactions of HMG 1 and 2 with negatively supercoiled DNA are modulated by their acidic C-terminal domains and involve cysteine residues in their HMG 1/2 boxes. , 1993, Biochemistry.

[70]  A. Harris,et al.  Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localisation of the gene to chromosome 3p24. , 1992, Nucleic acids research.

[71]  R. Hamanaka,et al.  Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells. , 1992, The Journal of biological chemistry.

[72]  N. Osheroff,et al.  Catalytic function of DNA topoisomerase II , 1991, BioEssays : news and reviews in molecular, cellular and developmental biology.

[73]  J. Wang,et al.  Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. , 1988, Proceedings of the National Academy of Sciences of the United States of America.