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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Scott W.  Hiebert

Scott W. Hiebert, Ph.D.

Associate Director for Basic Science Research and Shared Resources
Hortense B. Ingram Professor of Cancer Research
Professor of Biochemistry
Associate Professor of Medicine
Researcher

Contact Information:

Vanderbilt University Medical Center
512 Preston Building
Nashville, TN 37232-6838
615-936-3582

Research Description

The work in my laboratory focuses on determining the normal function of the AML1/RUNX1 transcription factor in the regulation of hematopoietic gene expression and the mechanism by which the t(8;21), inv(16), and the t(12;21) chromosomal translocations disrupt normal AML-1 function to promote acute leukemia. We have defined AML-1 as a transcription factor that binds the "enhancer core" motif, which regulates the expression of a large number of tissue specific genes. Transcriptional studies demonstrated that AML1 both activates and represses transcription, and that the translocation fusion proteins inhibit expression of AML1-dependent target genes. We have determined that the t(8;21) fusion protein, AML1/ETO, interacts with the mSin3 and nuclear hormone co-repressors that recruit histone deacetylases to repress transcription. This initial observation led us to demonstrate that the t(12;21) and inv(16) proteins also associate with co-repressors and histone deacetylases. Thus, we have identified a common mechanism for transcriptional repression for these three translocations. Given that these fusion proteins repress transcription and cause cancer, we asked whether they inhibit the expression of known tumor suppressor genes. We have identified 2 tumor suppressors that are regulated by these translocation fusion proteins (p19ARF and Neurofibromatosis-1), which regulate the p53 tumor suppressor and the Ras oncogene, respectively. We continue to use mouse models to dissect the molecular mechanisms by which these chromosomal translocation fusion proteins trigger acute leukemia.

In addition, we are examining the function of the ETO/MTG family of transcriptional co-repressors using gene ablation in the mouse. Both ETO (also known as MTG8) and MTG16 (a closely related family member) are disrupted by chromosomal translocations in acute myeloid leukemia (the t(8;21) and t(16;21), respectively). Moreover, MTG16 is commonly deleted in Breast cancer and ETO/MTG8 is mutated in colon cancer. Disruption of ETO caused perinatal lethality with some defects in gut development and we are still exploring the cause(s) of death. Disruption of MTG16 caused defects in stem cell functions and disruptions in cell fate decisions. Deletion of the third family member, Mtgr1, affected cell fate decisions in the small intestine. Global gene expression analysis is being used to dissect the transcriptional changes upon deletion of these master regulators and to relate the inactivation phenotypes to tumorigenesis. These studies have also linked the ETO family to the regulation of Wnt signaling and suggest that these factors function as tumor suppressors in Breast and Colon cancer.

Finally, we are extending our analysis of transcriptional control to the enzymes that are recruited by MTG family members and AML1/RUNX1. Specifically, we have inactivated Histone Deacetylase 3 in the mouse. We are currently dissecting the phenotypes associated with inactivation of this key regulator of chromatin structure and function. These phenotypes include cell cycle disruption, and wide spread changes in gene expression.

Publications
  • Farmer TE, Williams CS, Washington MK, Hiebert SW. Inactivation of the p19(ARF) tumor suppressor affects intestinal epithelial cell proliferation and integrity. J. Cell. Biochem. 2008 Aug 8/15/2008; 104(6): 2228-40. PMID: 18442038, PMCID: PMC3164503, DOI: 10.1002/jcb.21779, ISSN: 1097-4644.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18442038.
  • Hanson CA, Wood LD, Hiebert SW. Cellular stress triggers TEL nuclear export via two genetically separable pathways. J. Cell. Biochem. 2008 May 5/15/2008; 104(2): 488-98. PMID: 18022807, DOI: 10.1002/jcb.21637, ISSN: 1097-4644.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18022807.
  • Bhaskara S, Chyla BJ, Amann JM, Knutson SK, Cortez D, Sun ZW, Hiebert SW. Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control. Mol. Cell. 2008 Apr 4/11/2008; 30(1): 61-72. PMID: 18406327, PMCID: PMC2373760, PII: S1097-2765(08)00207-4, DOI: 10.1016/j.molcel.2008.02.030, ISSN: 1097-4164.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18406327.
  • Knutson SK, Chyla BJ, Amann JM, Bhaskara S, Huppert SS, Hiebert SW. Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks. EMBO J [print-electronic]. 2008 Apr 4/9/2008; 27(7): 1017-28. PMID: 18354499, PMCID: PMC2323257, PII: emboj200851, DOI: 10.1038/emboj.2008.51, ISSN: 1460-2075.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18354499.
  • Moore AC, Amann JM, Williams CS, Tahinci E, Farmer TE, Martinez JA, Yang G, Luce KS, Lee E, Hiebert SW. Myeloid translocation gene family members associate with T-cell factors (TCFs) and influence TCF-dependent transcription. Mol. Cell. Biol [print-electronic]. 2008 Feb; 28(3): 977-87. PMID: 18039847, PMCID: PMC2223385, PII: MCB.01242-07, DOI: 10.1128/MCB.01242-07, ISSN: 1098-5549.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18039847.
  • Yang G, Thompson MA, Brandt SJ, Hiebert SW. Histone deacetylase inhibitors induce the degradation of the t(8;21) fusion oncoprotein. Oncogene [print-electronic]. 2007 Jan 1/4/2007; 26(1): 91-101. PMID: 16799637, PII: 1209760, DOI: 10.1038/sj.onc.1209760, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16799637.
  • Reed-Inderbitzin E, Moreno-Miralles I, Vanden-Eynden SK, Xie J, Lutterbach B, Durst-Goodwin KL, Luce KS, Irvin BJ, Cleary ML, Brandt SJ, Hiebert SW. RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Oncogene [print-electronic]. 2006 Sep 9/21/2006; 25(42): 5777-86. PMID: 16652147, PII: 1209591, DOI: 10.1038/sj.onc.1209591, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16652147.
  • Martinez JA, Williams CS, Amann JM, Ellis TC, Moreno-Miralles I, Washington MK, Gregoli P, Hiebert SW. Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis. Gastroenterology. 2006 Aug; 131(2): 579-88. PMID: 16890610, PII: S0016-5085(06)01238-8, DOI: 10.1053/j.gastro.2006.06.009, ISSN: 0016-5085.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16890610.
  • Moreno-Miralles I, Pan L, Keates-Baleeiro J, Durst-Goodwin K, Yang C, Kim HG, Thompson MA, Klug CA, Cleveland JL, Hiebert SW. The inv(16) cooperates with ARF haploinsufficiency to induce acute myeloid leukemia. J. Biol. Chem [print-electronic]. 2005 Dec 12/2/2005; 280(48): 40097-103. PMID: 16199529, PII: M506855200, DOI: 10.1074/jbc.M506855200, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16199529.
  • Linggi BE, Brandt SJ, Sun ZW, Hiebert SW. Translating the histone code into leukemia. J. Cell. Biochem. 2005 Dec 12/1/2005; 96(5): 938-50. PMID: 16167339, DOI: 10.1002/jcb.20604, ISSN: 0730-2312.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16167339.
  • Amann JM, Chyla BJ, Ellis TC, Martinez A, Moore AC, Franklin JL, McGhee L, Meyers S, Ohm JE, Luce KS, Ouelette AJ, Washington MK, Thompson MA, King D, Gautam S, Coffey RJ, Whitehead RH, Hiebert SW. Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine. Mol. Cell. Biol. 2005 Nov; 25(21): 9576-85. PMID: 16227606, PMCID: PMC1265807, PII: 25/21/9576, DOI: 10.1128/MCB.25.21.9576-9585.2005, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16227606.
  • Ice RJ, Wildonger J, Mann RS, Hiebert SW. Comment on "Nervy links protein kinase A to plexin-mediated semaphorin repulsion". Science. 2005 Jul 7/22/2005; 309(5734): 558; author reply 558. PMID: 16040690, PII: 309/5734/558b, DOI: 10.1126/science.1108719, ISSN: 1095-9203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16040690.
  • Yang G, Khalaf W, van de Locht L, Jansen JH, Gao M, Thompson MA, van der Reijden BA, Gutmann DH, Delwel R, Clapp DW, Hiebert SW. Transcriptional repression of the Neurofibromatosis-1 tumor suppressor by the t(8;21) fusion protein. Mol. Cell. Biol. 2005 Jul; 25(14): 5869-79. PMID: 15988004, PMCID: PMC1168824, PII: 25/14/5869, DOI: 10.1128/MCB.25.14.5869-5879.2005, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15988004.
  • Yang G, Khalaf W, van de Locht L, Jansen JH, van der Reijden BA, Müller-Tidow C, Delwel HR, Serve H, Clapp DW, Hiebert SW. Epigenetic regulation of tumor suppressors in t(8:21)-containing AML. Ann. Hematol [print-electronic]. 2004 Jun; 83(6): 329-30. PMID: 15052372, DOI: 10.1007/s00277-003-0841-8, ISSN: 0939-5555.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15052372.
  • Durst KL, Hiebert SW. Role of RUNX family members in transcriptional repression and gene silencing. Oncogene. 2004 May 5/24/2004; 23(24): 4220-4. PMID: 15156176, PII: 1207122, DOI: 10.1038/sj.onc.1207122, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15156176.
  • Müller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Köhler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol. Cell. Biol. 2004 Apr; 24(7): 2890-904. PMID: 15024077, PMCID: PMC371102, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15024077.
  • Irvin BJ, Hiebert SW. AML-1 steps up to the platelets. Nature medicine. 2004 Mar; 10(3) Sect. 238,9.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14991045.
  • Yang G, Khalaf W, van de Locht L, Jansen JH, van der Reijden BA, Müller-Tidow C, Delwel HR, Serve H, Clapp DW, Hiebert SW. Epigenetic regulation of tumor suppressors in t(8:21)-containing AML. Ann. Hematol. 2004; 83 Suppl 1: S83. PMID: 15124686, DOI: 10.1007/s00277-004-0850-2, ISSN: 0939-5555.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15124686.
  • Irvin BJ, Wood LD, Wang L, Fenrick R, Sansam CG, Packham G, Kinch M, Yang E, Hiebert SW. TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL. J. Biol. Chem [print-electronic]. 2003 Nov 11/21/2003; 278(47): 46378-86. PMID: 12960174, PII: M305189200, DOI: 10.1074/jbc.M305189200, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12960174.
  • Wood LD, Irvin BJ, Nucifora G, Luce KS, Hiebert SW. Small ubiquitin-like modifier conjugation regulates nuclear export of TEL, a putative tumor suppressor. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2003 Mar 3/18/2003; 100(6): 3257-62. PMID: 12626745, PMCID: PMC152279, PII: 0637114100, DOI: 10.1073/pnas.0637114100, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12626745.
  • Hiebert SW, Reed-Inderbitzin EF, Amann J, Irvin B, Durst K, Linggi B. The t(8;21) fusion protein contacts co-repressors and histone deacetylases to repress the transcription of the p14ARF tumor suppressor. Blood Cells Mol. Dis. 2003 Mar; 30(2): 177-83. PMID: 12732181, PII: S1079979603000214, ISSN: 1079-9796.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12732181.
  • Durst KL, Lutterbach B, Kummalue T, Friedman AD, Hiebert SW. The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain. Mol. Cell. Biol. 2003 Jan; 23(2): 607-19. PMID: 12509458, PMCID: PMC151524, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12509458.
  • Barseguian K, Lutterbach B, Hiebert SW, Nickerson J, Lian JB, Stein JL, van Wijnen AJ, Stein GS. Multiple subnuclear targeting signals of the leukemia-related AML1/ETO and ETO repressor proteins. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Nov 11/26/2002; 99(24): 15434-9. PMID: 12427969, PMCID: PMC137734, PII: 242588499, DOI: 10.1073/pnas.242588499, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12427969.
  • de Guzman CG, Warren AJ, Zhang Z, Gartland L, Erickson P, Drabkin H, Hiebert SW, Klug CA. Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Mol. Cell. Biol. 2002 Aug; 22(15): 5506-17. PMID: 12101243, PMCID: PMC133929, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12101243.
  • King D, Yang G, Thompson MA, Hiebert SW. Loss of neurofibromatosis-1 and p19(ARF) cooperate to induce a multiple tumor phenotype. Oncogene. 2002 Jul 7/25/2002; 21(32): 4978-82. PMID: 12118376, DOI: 10.1038/sj.onc.1205632, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12118376.
  • Linggi B, Müller-Tidow C, van de Locht L, Hu M, Nip J, Serve H, Berdel WE, van der Reijden B, Quelle DE, Rowley JD, Cleveland J, Jansen JH, Pandolfi PP, Hiebert SW. The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nat. Med [print-electronic]. 2002 Jul; 8(7): 743-50. PMID: 12091906, PII: nm726, DOI: 10.1038/nm726, ISSN: 1078-8956.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12091906.
  • Eischen CM, Packham G, Nip J, Fee BE, Hiebert SW, Zambetti GP, Cleveland JL. Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1. Oncogene. 2001 Oct 10/25/2001; 20(48): 6983-93. PMID: 11704823, DOI: 10.1038/sj.onc.1204892, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11704823.
  • Amann JM, Nip J, Strom DK, Lutterbach B, Harada H, Lenny N, Downing JR, Meyers S, Hiebert SW. ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. Mol. Cell. Biol. 2001 Oct; 21(19): 6470-83. PMID: 11533236, PMCID: PMC99794, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11533236.
  • Hiebert SW, Lutterbach B, Amann J. Role of co-repressors in transcriptional repression mediated by the t(8;21), t(16;21), t(12;21), and inv(16) fusion proteins. Curr. Opin. Hematol. 2001 Jul; 8(4): 197-200. PMID: 11561155, ISSN: 1065-6251.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11561155.
  • Wang L, Hiebert SW. TEL contacts multiple co-repressors and specifically associates with histone deacetylase-3. Oncogene. 2001 Jun 6/21/2001; 20(28): 3716-25. PMID: 11439334, DOI: 10.1038/sj.onc.1204479, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11439334.
  • Nip J, Strom DK, Eischen CM, Cleveland JL, Zambetti GP, Hiebert SW. E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation. Oncogene. 2001 Feb 2/22/2001; 20(8): 910-20. PMID: 11314026, DOI: 10.1038/sj.onc.1204171, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11314026.
  • Melnick A, Carlile GW, McConnell MJ, Polinger A, Hiebert SW, Licht JD. AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein. Blood. 2000 Dec 12/1/2000; 96(12): 3939-47. PMID: 11090081, ISSN: 0006-4971.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11090081.
  • Fenrick R, Wang L, Nip J, Amann JM, Rooney RJ, Walker-Daniels J, Crawford HC, Hulboy DL, Kinch MS, Matrisian LM, Hiebert SW. TEL, a putative tumor suppressor, modulates cell growth and cell morphology of ras-transformed cells while repressing the transcription of stromelysin-1. Mol. Cell. Biol. 2000 Aug; 20(16): 5828-39. PMID: 10913166, PMCID: PMC86060, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10913166.
  • Lutterbach B, Hiebert SW. Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Gene. 2000 Mar 3/21/2000; 245(2): 223-35. PMID: 10717473, PII: S0378-1119(00)00014-7, ISSN: 0378-1119.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10717473.
  • Melnick AM, Westendorf JJ, Polinger A, Carlile GW, Arai S, Ball HJ, Lutterbach B, Hiebert SW, Licht JD. The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein. Mol. Cell. Biol. 2000 Mar; 20(6): 2075-86. PMID: 10688654, PMCID: PMC110824, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10688654.
  • Strom DK, Nip J, Westendorf JJ, Linggi B, Lutterbach B, Downing JR, Lenny N, Hiebert SW. Expression of the AML-1 oncogene shortens the G(1) phase of the cell cycle. J. Biol. Chem. 2000 Feb 2/4/2000; 275(5): 3438-45. PMID: 10652337, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10652337.
  • Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW. A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia. J. Biol. Chem. 2000 Jan 1/7/2000; 275(1): 651-6. PMID: 10617663, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10617663.
  • Meyers S, Hiebert SW. Alterations in subnuclear trafficking of nuclear regulatory factors in acute leukemia. J. Cell. Biochem. Suppl. 2000; Suppl 35: 93-8. PMID: 11389537, PII: 10.1002/1097-4644(2000)79:35+<93::AID-JCB1131>3.0.CO;2-4, ISSN: 0733-1959.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11389537.
  • Nip J, Hiebert SW. Topoisomerase IIalpha mediates E2F-1-induced chemosensitivity and is a target for p53-mediated transcriptional repression. Cell Biochem. Biophys. 2000; 33(2): 199-207. PMID: 11325040, PII: CBB:33:2:199, DOI: 10.1385/CBB:33:2:199, ISSN: 1085-9195.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11325040.
  • Lutterbach B, Hou Y, Durst KL, Hiebert SW. The inv(16) encodes an acute myeloid leukemia 1 transcriptional corepressor. Proc. Natl. Acad. Sci. U.S.A. 1999 Oct 10/26/1999; 96(22): 12822-7. PMID: 10536006, PMCID: PMC23113, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10536006.
  • Fenrick R, Amann JM, Lutterbach B, Wang L, Westendorf JJ, Downing JR, Hiebert SW. Both TEL and AML-1 contribute repression domains to the t(12;21) fusion protein. Mol. Cell. Biol. 1999 Oct; 19(10): 6566-74. PMID: 10490596, PMCID: PMC84626, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10490596.
  • Westendorf JJ, Mernaugh R, Hiebert SW. Identification and characterization of a protein containing formin homology (FH1/FH2) domains. Gene. 1999 May 5/31/1999; 232(2): 173-82. PMID: 10352228, PII: S0378111999001274, ISSN: 0378-1119.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10352228.
  • Westendorf JJ, Hiebert SW. Mammalian runt-domain proteins and their roles in hematopoiesis, osteogenesis, and leukemia. J. Cell. Biochem. 1999; Suppl 32-33: 51-8. PMID: 10629103, PII: 10.1002/(SICI)1097-4644(1999)75:32+<51::AID-JCB7>3.0.CO;2-S, ISSN: 0730-2312.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10629103.
  • Lutterbach B, Westendorf JJ, Linggi B, Patten A, Moniwa M, Davie JR, Huynh KD, Bardwell VJ, Lavinsky RM, Rosenfeld MG, Glass C, Seto E, Hiebert SW. ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Mol. Cell. Biol. 1998 Dec; 18(12): 7176-84. PMID: 9819404, PMCID: PMC109299, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9819404.
  • Petrovick MS, Hiebert SW, Friedman AD, Hetherington CJ, Tenen DG, Zhang DE. Multiple functional domains of AML1: PU.1 and C/EBPalpha synergize with different regions of AML1. Mol. Cell. Biol. 1998 Jul; 18(7): 3915-25. PMID: 9632776, PMCID: PMC108976, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9632776.
  • Ji C, Casinghino S, Chang DJ, Chen Y, Javed A, Ito Y, Hiebert SW, Lian JB, Stein GS, McCarthy TL, Centrella M. CBFa(AML/PEBP2)-related elements in the TGF-beta type I receptor promoter and expression with osteoblast differentiation. J. Cell. Biochem. 1998 Jun 6/1/1998; 69(3): 353-63. PMID: 9581873, PII: 10.1002/(SICI)1097-4644(19980601)69:3<353::AID-JCB12>3.0.CO;2-D, ISSN: 0730-2312.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9581873.
  • Lutterbach B, Sun D, Schuetz J, Hiebert SW. The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein. Mol. Cell. Biol. 1998 Jun; 18(6): 3604-11. PMID: 9584201, PMCID: PMC108942, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9584201.
  • Strom DK, Cleveland JL, Chellappan S, Nip J, Hiebert SW. E2F-1 and E2F-3 are functionally distinct in their ability to promote myeloid cell cycle progression and block granulocyte differentiation. Cell Growth Differ. 1998 Jan; 9(1): 59-69. PMID: 9438389, ISSN: 1044-9523.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9438389.
  • Westendorf JJ, Yamamoto CM, Lenny N, Downing JR, Selsted ME, Hiebert SW. The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Mol. Cell. Biol. 1998 Jan; 18(1): 322-33. PMID: 9418879, PMCID: PMC121499, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9418879.
  • Fenrick R, Hiebert SW. Role of histone deacetylases in acute leukemia. J. Cell. Biochem. Suppl. 1998; 30-31: 194-202. PMID: 9893271, ISSN: 0733-1959.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9893271.
  • Westendorf, J. J., Yamamoto, C. M., Lenny, N., Downing, J. R., Selsted, M.E., Hiebert, S. W. The t(8;21) fusion product, AML-1ETO, associates with C/EBP-a inhibits C/EBP-a dependent transcription, and blocks granulocytic differentiation. Mol. Cell. Biol. 1998; 18: 322-33.
    Available from: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9418879&dopt=Abstract.
  • Lenny N, Westendorf JJ, Hiebert SW. Transcriptional regulation during myelopoiesis. Mol. Biol. Rep. 1997 Aug; 24(3): 157-68. PMID: 9291089, ISSN: 0301-4851.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9291089.
  • Banerjee C, McCabe LR, Choi JY, Hiebert SW, Stein JL, Stein GS, Lian JB. Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J. Cell. Biochem. 1997 Jul 7/1/1997; 66(1): 1-8. PMID: 9215522, PII: 10.1002/(SICI)1097-4644(19970701)66:1<1::AID-JCB1>3.0.CO;2-V, ISSN: 0730-2312.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9215522.
  • Zeng C, van Wijnen AJ, Stein JL, Meyers S, Sun W, Shopland L, Lawrence JB, Penman S, Lian JB, Stein GS, Hiebert SW. Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors. Proc. Natl. Acad. Sci. U.S.A. 1997 Jun 6/24/1997; 94(13): 6746-51. PMID: 9192636, PMCID: PMC21229, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9192636.
  • Nip J, Strom DK, Fee BE, Zambetti G, Cleveland JL, Hiebert SW. E2F-1 cooperates with topoisomerase II inhibition and DNA damage to selectively augment p53-independent apoptosis. Mol. Cell. Biol. 1997 Mar; 17(3): 1049-56. PMID: 9032231, PMCID: PMC231829, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9032231.
  • Rhoades KL, Hetherington CJ, Rowley JD, Hiebert SW, Nucifora G, Tenen DG, Zhang DE. Synergistic up-regulation of the myeloid-specific promoter for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis. Proc. Natl. Acad. Sci. U.S.A. 1996 Oct 10/15/1996; 93(21): 11895-900. PMID: 8876234, PMCID: PMC38155, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8876234.
  • Meyers S, Lenny N, Sun W, Hiebert SW. AML-2 is a potential target for transcriptional regulation by the t(8;21) and t(12;21) fusion proteins in acute leukemia. Oncogene. 1996 Jul 7/18/1996; 13(2): 303-12. PMID: 8710369, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8710369.
  • Banerjee C, Hiebert SW, Stein JL, Lian JB, Stein GS. An AML-1 consensus sequence binds an osteoblast-specific complex and transcriptionally activates the osteocalcin gene. Proc. Natl. Acad. Sci. U.S.A. 1996 May 5/14/1996; 93(10): 4968-73. PMID: 8643513, PMCID: PMC39389, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8643513.
  • Hitomi M, Shu J, Strom D, Hiebert SW, Harter ML, Stacey DW. Prostaglandin A2 blocks the activation of G1 phase cyclin-dependent kinase without altering mitogen-activated protein kinase stimulation. J. Biol. Chem. 1996 Apr 4/19/1996; 271(16): 9376-83. PMID: 8621603, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8621603.
  • Hiebert SW, Sun W, Davis JN, Golub T, Shurtleff S, Buijs A, Downing JR, Grosveld G, Roussell MF, Gilliland DG, Lenny N, Meyers S. The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription. Mol. Cell. Biol. 1996 Apr; 16(4): 1349-55. PMID: 8657108, PMCID: PMC231119, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8657108.
  • Zhang DE, Hetherington CJ, Meyers S, Rhoades KL, Larson CJ, Chen HM, Hiebert SW, Tenen DG. CCAAT enhancer-binding protein (C/EBP) and AML1 (CBF alpha2) synergistically activate the macrophage colony-stimulating factor receptor promoter. Mol. Cell. Biol. 1996 Mar; 16(3): 1231-40. PMID: 8622667, PMCID: PMC231105, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8622667.
  • Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996 Jan 1/26/1996; 84(2): 321-30. PMID: 8565077, PII: S0092-8674(00)80986-1, ISSN: 0092-8674.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8565077.
  • Hiebert SW, Downing JR, Lenny N, Meyers S. Transcriptional regulation by the t(8;21) fusion protein, AML-1/ETO. Curr. Top. Microbiol. Immunol. 1996; 211: 253-8. PMID: 8585956, ISSN: 0070-217X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8585956.
  • Frank R, Zhang J, Uchida H, Meyers S, Hiebert SW, Nimer SD. The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B. Oncogene. 1995 Dec 12/21/1995; 11(12): 2667-74. PMID: 8545124, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8545124.
  • Hiebert SW, Packham G, Strom DK, Haffner R, Oren M, Zambetti G, Cleveland JL. E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol. 1995 Dec; 15(12): 6864-74. PMID: 8524253, PMCID: PMC230941, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8524253.
  • Lenny N, Meyers S, Hiebert SW. Functional domains of the t(8;21) fusion protein, AML-1/ETO. Oncogene. 1995 Nov 11/2/1995; 11(9): 1761-9. PMID: 7478604, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/7478604.
  • Shurtleff SA, Meyers S, Hiebert SW, Raimondi SC, Head DR, Willman CL, Wolman S, Slovak ML, Carroll AJ, Behm F. Heterogeneity in CBF beta/MYH11 fusion messages encoded by the inv(16)(p13q22) and the t(16;16)(p13;q22) in acute myelogenous leukemia. Blood. 1995 Jun 6/15/1995; 85(12): 3695-703. PMID: 7780153, ISSN: 0006-4971.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/7780153.
  • Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD, Gilliland DG. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. U.S.A. 1995 May 5/23/1995; 92(11): 4917-21. PMID: 7761424, PMCID: PMC41818, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/7761424.
  • Meyers S, Lenny N, Hiebert SW. The t(8;21) fusion protein interferes with AML-1B-dependent transcriptional activation. Mol. Cell. Biol. 1995 Apr; 15(4): 1974-82. PMID: 7891692, PMCID: PMC230424, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/7891692.
  • Meyers S, Hiebert SW. Indirect and direct disruption of transcriptional regulation in cancer: E2F and AML-1. Crit. Rev. Eukaryot. Gene Expr. 1995; 5(3-4): 365-83. PMID: 8834231, ISSN: 1045-4403.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8834231.
  • Dobrowolski SF, Stacey DW, Harter ML, Stine JT, Hiebert SW. An E2F dominant negative mutant blocks E1A induced cell cycle progression. Oncogene. 1994 Sep; 9(9): 2605-12. PMID: 8058324, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8058324.
  • Roussel MF, Davis JN, Cleveland JL, Ghysdael J, Hiebert SW. Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1. Oncogene. 1994 Feb; 9(2): 405-15. PMID: 8290253, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8290253.
  • Meyers S, Downing JR, Hiebert SW. Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein-protein interactions. Mol. Cell. Biol. 1993 Oct; 13(10): 6336-45. PMID: 8413232, PMCID: PMC364692, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8413232.
  • Hiebert SW. Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression. Mol. Cell. Biol. 1993 Jun; 13(6): 3384-91. PMID: 8497257, PMCID: PMC359800, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8497257.
  • Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993 Mar; 7(3): 331-42. PMID: 8449399, ISSN: 0890-9369.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8449399.
  • Roussel MF, Davis JN, Cleveland JL, Hiebert SW. Duel Control of myc Expression Through a Single DNA Binding Site targeted by ets Family Proteins and E2F-1. Oncogene. 1993; 9: 405-15.
  • Hiebert SW, Chellappan SP, Horowitz JM, Nevins JR. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992 Feb; 6(2): 177-85. PMID: 1531329, ISSN: 0890-9369.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/1531329.
  • Hiebert SW, Blake M, Azizkhan J, Nevins JR. Role of E2F transcription factor in E1A-mediated trans activation of cellular genes. J. Virol. 1991 Jul; 65(7): 3547-52. PMID: 1828272, PMCID: PMC241350, ISSN: 0022-538X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/1828272.
  • Mudryj M, Devoto SH, Hiebert SW, Hunter T, Pines J, Nevins JR. Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell. 1991 Jun 6/28/1991; 65(7): 1243-53. PMID: 1829647, PII: 0092-8674(91)90019-U, ISSN: 0092-8674.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/1829647.
  • Mudryj M, Hiebert SW, Nevins JR. A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J. 1990 Jul; 9(7): 2179-84. PMID: 2141565, PMCID: PMC551940, ISSN: 0261-4189.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/2141565.
  • Ng DT, Hiebert SW, Lamb RA. Different roles of individual N-linked oligosaccharide chains in folding, assembly, and transport of the simian virus 5 hemagglutinin-neuraminidase. Mol. Cell. Biol. 1990 May; 10(5): 1989-2001. PMID: 2183015, PMCID: PMC360545, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/2183015.
  • Hiebert SW, Lipp M, Nevins JR. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor. Proc. Natl. Acad. Sci. U.S.A. 1989 May; 86(10): 3594-8. PMID: 2524830, PMCID: PMC287184, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/2524830.
  • Hiebert SW, Lamb RA. Cell surface expression of glycosylated, nonglycosylated, and truncated forms of a cytoplasmic protein pyruvate kinase. J. Cell Biol. 1988 Sep; 107(3): 865-76. PMID: 3047152, PMCID: PMC2115283, ISSN: 0021-9525.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/3047152.
  • Hiebert SW, Richardson CD, Lamb RA. Cell surface expression and orientation in membranes of the 44-amino-acid SH protein of simian virus 5. J. Virol. 1988 Jul; 62(7): 2347-57. PMID: 2836617, PMCID: PMC253391, ISSN: 0022-538X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/2836617.
  • Hiebert SW, Williams MA, Lamb RA. Nucleotide sequence of RNA segment 7 of influenza B/Singapore/222/79: maintenance of a second large open reading frame. Virology. 1986 Dec; 155(2): 747-51. PMID: 3788064, ISSN: 0042-6822.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/3788064.
  • Paterson RG, Hiebert SW, Lamb RA. Expression at the cell surface of biologically active fusion and hemagglutinin/neuraminidase proteins of the paramyxovirus simian virus 5 from cloned cDNA. Proc. Natl. Acad. Sci. U.S.A. 1985 Nov; 82(22): 7520-4. PMID: 3865176, PMCID: PMC390848, ISSN: 0027-8424.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/3865176.
  • Hiebert SW, Paterson RG, Lamb RA. Identification and predicted sequence of a previously unrecognized small hydrophobic protein, SH, of the paramyxovirus simian virus 5. J. Virol. 1985 Sep; 55(3): 744-51. PMID: 4020965, PMCID: PMC255058, ISSN: 0022-538X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/4020965.
  • Hiebert SW, Paterson RG, Lamb RA. Hemagglutinin-neuraminidase protein of the paramyxovirus simian virus 5: nucleotide sequence of the mRNA predicts an N-terminal membrane anchor. J. Virol. 1985 Apr; 54(1): 1-6. PMID: 3973974, PMCID: PMC254752, ISSN: 0022-538X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/3973974.