Nucleic Acids Research, 1995, Vol. 23, No. 10 1686-1690
© 1995
MOLECULAR BIOLOGY |
A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins
Biochemistry of the Cell Nucleus London WC2A 3PX, UK 1Molecular Endocrinology Laboratories, Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields London WC2A 3PX, UK
* To whom correspondence should be addressed
Received February 22, 1995. Revised April 5, 1995. Accepted April 5, 1995.
A number of proteins have been rendered functionally oestrogen-dependent by fusion with the hormone-binding domain of the oestrogen receptor. There are, however, several significant disadvantages with such fusion proteins. First, their use In cells in vitro requires phenol red-free medium and laborious stripping of steroid hormones from serum In order to avoid constitutive activation. Secondly, control of oestrogen receptor fusion proteins In vivo is precluded by high endogenous levels of circulating oestrogens. Thirdly, the hormone-binding domain of the oestrogen receptor functions as a hormone-dependent transcriptional activation domain making interpretation of fusions with transcription factors problematical. In order to overcome these drawbacks we have used a transcrip-tlonally inactive mutant of the murine oestrogen receptor which is unable to bind oestrogen yet retains normal affinity for the synthetic ligand, 4-hydroxyta-moxifen. When the hormone-binding domain of this mutant oestrogen receptor is fused to the C-terminus of the c-Myc protein, Myc-induced proliferation and apoptosis In fibroblasts becomes dependent on 4-hydroxytamoxifen, but remains refractory to 17ß-oestradlol.
+Present address: McMahon Laboratory, Biological Laboratories, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
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K. W. Vance, S. Carreira, G. Brosch, and C. R. Goding Tbx2 Is Overexpressed and Plays an Important Role in Maintaining Proliferation and Suppression of Senescence in Melanomas Cancer Res., March 15, 2005; 65(6): 2260 - 2268. [Abstract] [Full Text] [PDF]
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S. Demaria, F. R. Santori, B. Ng, L. Liebes, S. C. Formenti, and S. Vukmanovic Select forms of tumor cell apoptosis induce dendritic cell maturation J. Leukoc. Biol., March 1, 2005; 77(3): 361 - 368. [Abstract] [Full Text] [PDF]
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J. Y. Zhang, S. Tao, R. Kimmel, and P. A. Khavari CDK4 regulation by TNFR1 and JNK is required for NF-{kappa}B-mediated epidermal growth control J. Cell Biol., February 14, 2005; 168(4): 561 - 566. [Abstract] [Full Text] [PDF]
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A. R. Jazirehi, S. Huerta-Yepez, G. Cheng, and B. Bonavida Rituximab (Chimeric Anti-CD20 Monoclonal Antibody) Inhibits the Constitutive Nuclear Factor-{kappa}B Signaling Pathway in Non-Hodgkin's Lymphoma B-Cell Lines: Role in Sensitization to Chemotherapeutic Drug-induced Apoptosis Cancer Res., January 1, 2005; 65(1): 264 - 276. [Abstract] [Full Text] [PDF]
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G. De Vita, L. Bauer, V. M. C. da Costa, M. De Felice, M. G. Baratta, M. De Menna, and R. Di Lauro Dose-Dependent Inhibition of Thyroid Differentiation by RAS Oncogenes Mol. Endocrinol., January 1, 2005; 19(1): 76 - 89. [Abstract] [Full Text] [PDF]
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H.-J. Choi and T. E. Smithgall HIV-1 Nef Promotes Survival of TF-1 Macrophages by Inducing Bcl-XL Expression in an Extracellular Signal-regulated Kinase-dependent Manner J. Biol. Chem., December 3, 2004; 279(49): 51688 - 51696. [Abstract] [Full Text] [PDF]
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J. A. Nilsson, L. M. Nilsson, U. Keller, Y. Yokota, K. Boyd, and J. L. Cleveland Id2 Is Dispensable for Myc-Induced Lymphomagenesis Cancer Res., October 15, 2004; 64(20): 7296 - 7301. [Abstract] [Full Text] [PDF]
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R. Drissen, R.-J. Palstra, N. Gillemans, E. Splinter, F. Grosveld, S. Philipsen, and W. de Laat The active spatial organization of the {beta}-globin locus requires the transcription factor EKLF Genes & Dev., October 15, 2004; 18(20): 2485 - 2490. [Abstract] [Full Text] [PDF]
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M. S. Ricci, Z. Jin, M. Dews, D. Yu, A. Thomas-Tikhonenko, D. T. Dicker, and W. S. El-Deiry Direct Repression of FLIP Expression by c-myc Is a Major Determinant of TRAIL Sensitivity Mol. Cell. Biol., October 1, 2004; 24(19): 8541 - 8555. [Abstract] [Full Text] [PDF]
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H. M. Bill, B. Knudsen, S. L. Moores, S. K. Muthuswamy, V. R. Rao, J. S. Brugge, and C. K. Miranti Epidermal Growth Factor Receptor-Dependent Regulation of Integrin-Mediated Signaling and Cell Cycle Entry in Epithelial Cells Mol. Cell. Biol., October 1, 2004; 24(19): 8586 - 8599. [Abstract] [Full Text] [PDF]
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U. E. Knies-Bamforth, S. B. Fox, R. Poulsom, G. I. Evan, and A. L. Harris c-Myc Interacts with Hypoxia to Induce Angiogenesis In vivo by a Vascular Endothelial Growth Factor-Dependent Mechanism Cancer Res., September 15, 2004; 64(18): 6563 - 6570. [Abstract] [Full Text] [PDF]
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 A. I. Rojo, M. Salinas, D. Martin, R. Perona, and A. Cuadrado Regulation of Cu/Zn-Superoxide Dismutase Expression via the Phosphatidylinositol 3 Kinase/Akt Pathway and Nuclear Factor-{kappa}B J. Neurosci., August 18, 2004; 24(33): 7324 - 7334. [Abstract] [Full Text] [PDF]
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 S. M. Janes, T. A. Ofstad, D. H. Campbell, F. M. Watt, and D. M. Prowse Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt J. Cell Sci., August 15, 2004; 117(18): 4157 - 4168. [Abstract] [Full Text] [PDF]
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A. Thomas-Tikhonenko, I. Viard-Leveugle, M. Dews, P. Wehrli, C. Sevignani, D. Yu, S. Ricci, W. el-Deiry, B. Aronow, G. Kaya, et al. Myc-Transformed Epithelial Cells Down-Regulate Clusterin, Which Inhibits Their Growth in Vitro and Carcinogenesis in Vivo Cancer Res., May 1, 2004; 64(9): 3126 - 3136. [Abstract] [Full Text] [PDF]
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O. G. Rossler and G. Thiel Brain-derived neurotrophic factor-, epidermal growth factor-, or A-Raf-induced growth of HaCaT keratinocytes requires extracellular signal-regulated kinase Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1118 - C1129. [Abstract] [Full Text] [PDF]
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C. L. Celso, D. M. Prowse, and F. M. Watt Transient activation of {beta}-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours Development, April 15, 2004; 131(8): 1787 - 1799. [Abstract] [Full Text] [PDF]
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S.-C. Teng, Y.-Y. Chen, Y.-N. Su, P.-C. Chou, Y.-C. Chiang, S.-F. Tseng, and K.-J. Wu Direct Activation of HSP90A Transcription by c-Myc Contributes to c-Myc-induced Transformation J. Biol. Chem., April 9, 2004; 279(15): 14649 - 14655. [Abstract] [Full Text] [PDF]
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A. Glading, R. J. Bodnar, I. J. Reynolds, H. Shiraha, L. Satish, D. A. Potter, H. C. Blair, and A. Wells Epidermal Growth Factor Activates m-Calpain (Calpain II), at Least in Part, by Extracellular Signal-Regulated Kinase-Mediated Phosphorylation Mol. Cell. Biol., March 15, 2004; 24(6): 2499 - 2512. [Abstract] [Full Text] [PDF]
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D. J. Murphy, L. B. Swigart, M. A. Israel, and G. I. Evan Id2 Is Dispensable for Myc-Induced Epidermal Neoplasia Mol. Cell. Biol., March 1, 2004; 24(5): 2083 - 2090. [Abstract] [Full Text] [PDF]
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J. A. Nilsson, K. H. Maclean, U. B. Keller, H. Pendeville, T. A. Baudino, and J. L. Cleveland Mnt Loss Triggers Myc Transcription Targets, Proliferation, Apoptosis, and Transformation Mol. Cell. Biol., February 15, 2004; 24(4): 1560 - 1569. [Abstract] [Full Text] [PDF]
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J. K. Brunelle, M. T. Santore, G. R. S. Budinger, Y. Tang, T. A. Barrett, W.-X. Zong, E. Kandel, B. Keith, M. C. Simon, C. B. Thompson, et al. c-Myc Sensitization to Oxygen Deprivation-induced Cell Death Is Dependent on Bax/Bak, but Is Independent of p53 and Hypoxia-inducible Factor-1 J. Biol. Chem., February 6, 2004; 279(6): 4305 - 4312. [Abstract] [Full Text] [PDF]
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B. B. Zeisig, T. Milne, M.-P. Garcia-Cuellar, S. Schreiner, M.-E. Martin, U. Fuchs, A. Borkhardt, S. K. Chanda, J. Walker, R. Soden, et al. Hoxa9 and Meis1 Are Key Targets for MLL-ENL-Mediated Cellular Immortalization Mol. Cell. Biol., January 15, 2004; 24(2): 617 - 628. [Abstract] [Full Text] [PDF]
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 J. M. Lawrence, D. J. Keegan, E. M. Muir, P. J. Coffey, J. H. Rogers, M. J. Wilby, J. W. Fawcett, and R. D. Lund Transplantation of Schwann Cell Line Clones Secreting GDNF or BDNF into the Retinas of Dystrophic Royal College of Surgeons Rats Invest. Ophthalmol. Vis. Sci., January 1, 2004; 45(1): 267 - 274. [Abstract] [Full Text] [PDF]
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 A. Ouvrard-Pascaud, S. Puttini, Y. Sainte-Marie, R. Athman, V. Fontaine, F. Cluzeaud, N. Farman, M.-E. Rafestin-Oblin, M. Blot-Chabaud, and F. Jaisser Conditional gene expression in renal collecting duct epithelial cells: use of the inducible Cre-lox system Am J Physiol Renal Physiol, January 1, 2004; 286(1): F180 - F187. [Abstract] [Full Text] [PDF]
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K. Balmanno, T. Millar, M. McMahon, and S. J. Cook {Delta}Raf-1:ER* Bypasses the Cyclic AMP Block of Extracellular Signal-Regulated Kinase 1 and 2 Activation but Not CDK2 Activation or Cell Cycle Reentry Mol. Cell. Biol., December 15, 2003; 23(24): 9303 - 9317. [Abstract] [Full Text] [PDF]
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M. J. McConnell, N. Chevallier, W. Berkofsky-Fessler, J. M. Giltnane, R. B. Malani, L. M. Staudt, and J. D. Licht Growth Suppression by Acute Promyelocytic Leukemia-Associated Protein PLZF Is Mediated by Repression of c-myc Expression Mol. Cell. Biol., December 15, 2003; 23(24): 9375 - 9388. [Abstract] [Full Text] [PDF]
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Y. Feng, N. Lee, and E. R. Fearon TIP49 Regulates {beta}-Catenin-Mediated Neoplastic Transformation and T-Cell Factor Target Gene Induction via Effects on Chromatin Remodeling Cancer Res., December 15, 2003; 63(24): 8726 - 8734. [Abstract] [Full Text] [PDF]
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K. H. Maclean, U. B. Keller, C. Rodriguez-Galindo, J. A. Nilsson, and J. L. Cleveland c-Myc Augments Gamma Irradiation-Induced Apoptosis by Suppressing Bcl-XL Mol. Cell. Biol., October 15, 2003; 23(20): 7256 - 7270. [Abstract] [Full Text] [PDF]
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S. Maruo, E. Johannsen, D. Illanes, A. Cooper, and E. Kieff Epstein-Barr Virus Nuclear Protein EBNA3A Is Critical for Maintaining Lymphoblastoid Cell Line Growth J. Virol., October 1, 2003; 77(19): 10437 - 10447. [Abstract] [Full Text] [PDF]
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