FOXM1, a typical proliferation-associated transcription factor

Abstract FOXM1 is a typical proliferation-associated transcription factor: it stimulates proliferation by promoting S-phase entry as well as M-phase entry and is involved in proper execution of mitosis. Accordingly, FOXM1 regulates genes that control G1/S-transition, S-phase progression, G2/M-transition and M-phase progression. Consistently, its expression and its activity are antagonistically regulated by many important proliferation and anti-proliferation signals. Furthermore, FOXM1 is implicated in tumorigenesis and contributes to both tumor initiation and progression. In addition to its function as a conventional transcription factor, FOXM1 transactivates the human c-myc P1 and P2 promoters directly via their TATA-boxes by a new transactivation mechanism, which it also employs for transactivation of the human c-fos, hsp70 and histone H2B/a promoters. This review summarizes the current knowledge on FOXM1, in particular its two different transactivation mechanisms, the regulation of its transcriptional activity by proliferation versus anti-proliferation signals and its function in normal cell cycle progression and tumorigenesis.

[1]  M. Karin,et al.  AP-1 in cell proliferation and survival , 2001, Oncogene.

[2]  René H Medema,et al.  FoxM1: at the crossroads of ageing and cancer. , 2007, Biochimica et biophysica acta.

[3]  R. Costa,et al.  Premature Expression of the Winged Helix Transcription Factor HFH-11B in Regenerating Mouse Liver Accelerates Hepatocyte Entry into S Phase , 1999, Molecular and Cellular Biology.

[4]  S. Burley,et al.  Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5 , 1993, Nature.

[5]  Steven P Gygi,et al.  Large-scale characterization of HeLa cell nuclear phosphoproteins. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Costa.  FoxM1 dances with mitosis , 2005, Nature Cell Biology.

[7]  David E. Misek,et al.  Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. , 2003, The American journal of pathology.

[8]  M. Becich,et al.  Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process , 2007, BMC Cancer.

[9]  Hans Clevers,et al.  FoxM1 is required for execution of the mitotic programme and chromosome stability , 2005, Nature Cell Biology.

[10]  Zhiping Weng,et al.  Global mapping of c-Myc binding sites and target gene networks in human B cells , 2006, Proceedings of the National Academy of Sciences.

[11]  E. Lam,et al.  The Forkhead Box M1 Protein Regulates the Transcription of the Estrogen Receptor α in Breast Cancer Cells* , 2006, Journal of Biological Chemistry.

[12]  A. Gartel,et al.  Identification of a chemical inhibitor of the oncogenic transcription factor forkhead box M1. , 2006, Cancer research.

[13]  I. Wierstra,et al.  FOXM1c transactivates the human c‐myc promoter directly via the two TATA boxes P1 and P2 , 2006, The FEBS journal.

[14]  J. Bishop,et al.  The MYC protein activates transcription of the alpha‐prothymosin gene. , 1991, The EMBO journal.

[15]  Robert H. Costa,et al.  Forkhead Box M1B Transcriptional Activity Requires Binding of Cdk-Cyclin Complexes for Phosphorylation-Dependent Recruitment of p300/CBP Coactivators , 2004, Molecular and Cellular Biology.

[16]  Raymond Sawaya,et al.  FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. , 2006, Cancer research.

[17]  R. Costa,et al.  Recruitment of p 300 / CBP Coactivators for Phosphorylation-Dependent Requires Binding of Cdk-Cyclin Complexes Forkhead Box M 1 B Transcriptional Activity , 2004 .

[18]  C. Ball,et al.  Identification of genes periodically expressed in the human cell cycle and their expression in tumors. , 2002, Molecular biology of the cell.

[19]  P. Sharp,et al.  Pre-bending of a promoter sequence enhances affinity for the TATA-binding factor , 1995, Nature.

[20]  C. Pilarsky,et al.  Identification and validation of commonly overexpressed genes in solid tumors by comparison of microarray data. , 2004, Neoplasia.

[21]  H. Clevers,et al.  The winged-helix transcription factor Trident is expressed in actively dividing lymphocytes. , 1997, Immunobiology.

[22]  K. Aldape,et al.  Aberrant FoxM1B expression increases matrix metalloproteinase-2 transcription and enhances the invasion of glioma cells , 2007, Oncogene.

[23]  N. Davidson,et al.  The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer. , 2007, Gastroenterology.

[24]  M. Tretiakova,et al.  The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. , 2006, Cancer research.

[25]  H. Kiyokawa,et al.  The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  I. Wierstra,et al.  FOXM1c is activated by cyclin E/Cdk2, cyclin A/Cdk2, and cyclin A/Cdk1, but repressed by GSK-3alpha. , 2006, Biochemical and biophysical research communications.

[27]  Yiwei Li,et al.  Gene expression profiling revealed novel molecular targets of docetaxel and estramustine combination treatment in prostate cancer cells , 2005, Molecular Cancer Therapeutics.

[28]  M. Henriksson,et al.  Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation , 1999, Oncogene.

[29]  J. Locker,et al.  Aging does not reduce the hepatocyte proliferative response of mice to the primary mitogen TCPOBOP , 2004, Hepatology.

[30]  H. Clevers,et al.  The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization. , 1997, Genomics.

[31]  J. Alves,et al.  FOXM1c and Sp1 transactivate the P1 and P2 promoters of human c-myc synergistically. , 2007, Biochemical and biophysical research communications.

[32]  R. Costa,et al.  Increased expression of hepatocyte nuclear factor 6 stimulates hepatocyte proliferation during mouse liver regeneration. , 2006, Gastroenterology.

[33]  L. Lim,et al.  Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[34]  P. Carlsson,et al.  Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending. , 1994, The EMBO journal.

[35]  J. Shim,et al.  Temporal expression changes during differentiation of neural stem cells derived from mouse embryonic stem cell , 2004, Journal of cellular biochemistry.

[36]  Giacomo Finocchiaro,et al.  Myc-binding-site recognition in the human genome is determined by chromatin context , 2006, Nature Cell Biology.

[37]  L. Lim,et al.  Hepatocyte Nuclear Factor 3 / fork head Homolog 11 Is Expressed in Proliferating Epithelial and Mesenchymal Cells of Embryonic and Adult Tissues , 1996 .

[38]  M. Teh,et al.  FOXM 1 Is a Downstream Target of Gli 1 in Basal Cell Carcinomas 1 , 2002 .

[39]  Yiwei Li,et al.  Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells , 2005, BMC Cancer.

[40]  M. Gannon,et al.  The FoxM1 Transcription Factor Is Required to Maintain Pancreatic β-Cell Mass , 2006 .

[41]  L. M. Facchini,et al.  The molecular role of Myc in growth and transformation: recent discoveries lead to new insights , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  R. Costa,et al.  Increased levels of forkhead box M1B transcription factor in transgenic mouse hepatocytes prevent age-related proliferation defects in regenerating liver , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Vladimir Petrovic,et al.  A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment. , 2007, The Journal of clinical investigation.

[44]  M. Follettie,et al.  Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe. , 2005, Cancer research.

[45]  Yusuke Nakamura,et al.  Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection , 2004, Oncogene.

[46]  Günter Lepperdinger,et al.  Profiling molecular targets of TGF-β1 in prostate fibroblast-to-myofibroblast transdifferentiation , 2005, Mechanisms of Ageing and Development.

[47]  Andrea Cocito,et al.  Genomic targets of the human c-Myc protein. , 2003, Genes & development.

[48]  L. Gerace,et al.  Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[49]  S. Kalinin,et al.  Sustained hepatic expression of FoxM1B in transgenic mice has minimal effects on hepatocellular carcinoma development but increases cell proliferation rates in preneoplastic and early neoplastic lesions , 2003, Oncogene.

[50]  M. Teh,et al.  FOXM1 is a downstream target of Gli1 in basal cell carcinomas. , 2002, Cancer research.

[51]  I. Wierstra,et al.  The central domain of transcription factor FOXM1c directly interacts with itself in vivo and switches from an essential to an inhibitory domain depending on the FOXM1c binding site , 2007, Biological chemistry.

[52]  R. Costa,et al.  Growth hormone stimulates proliferation of old‐aged regenerating liver through forkhead box m1b , 2003, Hepatology.

[53]  Gavin D. Grant,et al.  Common markers of proliferation , 2006, Nature Reviews Cancer.

[54]  F. Watt,et al.  Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment , 2003, Development.

[55]  A. Malik,et al.  Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box m1 transcription factor , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[56]  B. Lüscher,et al.  Regulation of the transcription factor FOXM1c by Cyclin E/CDK2 , 2006, FEBS letters.

[57]  I. Wierstra,et al.  Despite its strong transactivation domain, transcription factor FOXM1c is kept almost inactive by two different inhibitory domains , 2006, Biological chemistry.

[58]  R. Costa,et al.  Chk2 Mediates Stabilization of the FoxM1 Transcription Factor To Stimulate Expression of DNA Repair Genes , 2006, Molecular and Cellular Biology.

[59]  I. Wierstra,et al.  The c-myc promoter: still MysterY and challenge. , 2008, Advances in cancer research.

[60]  G. Gusarova,et al.  The Forkhead Box M1 Transcription Factor Is Essential for Embryonic Development of Pulmonary Vasculature* , 2005, Journal of Biological Chemistry.

[61]  J. Massagué,et al.  G1 cell-cycle control and cancer , 2004, Nature.

[62]  M. Skinner,et al.  Role of winged helix transcription factor (WIN) in the regulation of Sertoli cell differentiated functions: WIN acts as an early event gene for follicle-stimulating hormone. , 2000, Endocrinology.

[63]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[64]  I. Wierstra,et al.  Transcription factor FOXM1c is repressed by RB and activated by cyclin D1/Cdk4 , 2006, Biological chemistry.

[65]  A. Datta,et al.  Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor. , 2004, Genes & development.

[66]  H. Clevers,et al.  Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident , 1998, Current Biology.

[67]  Vladimir Petrovic,et al.  Forkhead Box M1 Regulates the Transcriptional Network of Genes Essential for Mitotic Progression and Genes Encoding the SCF (Skp2-Cks1) Ubiquitin Ligase , 2005, Molecular and Cellular Biology.

[68]  David E. Misek,et al.  Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis. , 2001, Cancer research.

[69]  中村 透.  Genome-wide cDNA microarray analysis of gene-expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection , 2004 .

[70]  L. Gerace,et al.  Identification of novel M phase phosphoproteins by expression cloning. , 1996, Molecular biology of the cell.

[71]  D. Botstein,et al.  Diversity of gene expression in adenocarcinoma of the lung , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[72]  R. Costa,et al.  New and unexpected: forkhead meets ARF. , 2005, Current opinion in genetics & development.

[73]  H. Clevers,et al.  The winged-helix transcription factor Trident is expressed in cycling cells. , 1997, Nucleic acids research.

[74]  C. Perou,et al.  Molecular portraits and the family tree of cancer , 2002, Nature Genetics.

[75]  A. Moustakas,et al.  Hyaluronan Fragments Induce Endothelial Cell Differentiation in a CD44- and CXCL1/GRO1-dependent Manner*boxs , 2005, Journal of Biological Chemistry.

[76]  L. Penn,et al.  The myc oncogene: MarvelouslY Complex. , 2002, Advances in cancer research.

[77]  Chong Sze Tong,et al.  Over‐expression of FoxM1 stimulates cyclin B1 expression , 2001, FEBS letters.

[78]  Zhiwei Wang,et al.  Gene expression profiling revealed survivin as a target of 3,3'-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells. , 2006, Cancer research.

[79]  Yusuke Nakamura,et al.  Genome‐wide analysis of gene expression in human intrahepatic cholangiocarcinoma , 2005, Hepatology.

[80]  R. Costa,et al.  Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. , 2006, Cancer research.

[81]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[82]  K. Yao,et al.  Molecular Analysis of a Novel Winged Helix Protein, WIN , 1997, The Journal of Biological Chemistry.

[83]  Yan Zhou,et al.  Rapid hepatocyte nuclear translocation of the Forkhead Box M1B (FoxM1B) transcription factor caused a transient increase in size of regenerating transgenic hepatocytes. , 2003, Gene expression.

[84]  D. Moore,et al.  Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration , 2006, Science.

[85]  G. Gusarova,et al.  Ubiquitous Expression of the Forkhead Box M1B Transgene Accelerates Proliferation of Distinct Pulmonary Cell Types following Lung Injury* , 2003, Journal of Biological Chemistry.

[86]  T. Tsunoda,et al.  Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. , 2001, Cancer research.

[87]  R. Costa,et al.  Earlier expression of the transcription factor HFH‐11B diminishes induction of p21CIP1/WAF1 levels and accelerates mouse hepatocyte entry into S‐phase following carbon tetrachloride liver injury , 2001, Hepatology.

[88]  D. Lockhart,et al.  Mitotic misregulation and human aging. , 2000, Science.

[89]  R. Frey,et al.  Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury. , 2006, The Journal of clinical investigation.

[90]  R. Costa,et al.  Transcription factors in liver development, differentiation, and regeneration , 2003, Hepatology.

[91]  E. Greer,et al.  FOXO transcription factors at the interface between longevity and tumor suppression , 2005, Oncogene.

[92]  M. Gannon,et al.  The FoxM1 transcription factor is required to maintain pancreatic beta-cell mass. , 2006, Molecular endocrinology.

[93]  K. Kaestner,et al.  The mouse Forkhead Box m1 transcription factor is essential for hepatoblast mitosis and development of intrahepatic bile ducts and vessels during liver morphogenesis. , 2004, Developmental biology.

[94]  G. Adami,et al.  Increased Hepatic Forkhead Box M1B (FoxM1B) Levels in Old-aged Mice Stimulated Liver Regeneration through Diminished p27Kip1 Protein Levels and Increased Cdc25B Expression* , 2002, The Journal of Biological Chemistry.

[95]  A. Cheung,et al.  Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c , 2005, Journal of Cell Science.