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Abstract:

Fulvestrant, a selective estrogen receptor down-regulator (SERD) is a pure competitive antagonist of estrogen receptor alpha (ERα). Fulvestrant binds ERα and reduces the receptor's half-life by increasing protein turnover, however, its mechanism of action is not fully understood. In this study, we show that removal of the ERα nuclear localization sequence (ERδNLS) resulted in a predominantly cytoplasmic ERα that was degraded in response to 17-β-estradiol (E2) but was resistant to degradation by fulvestrant. ERδNLS bound the ligands and exhibited receptor interaction similar to ERα, indicating that the lack of degradation was not due to disruption of these processes. Forcing ERδNLS into the nucleus with a heterologous SV40-NLS did not restore degradation, suggesting that the NLS domain itself, and not merely receptor localization, is critical for fulvestrant-induced ERα degradation. Indeed, cloning of the endogenous ERα NLS onto the N-terminus of ERδNLS significantly restored both its nuclear localization and turnover in response to fulvestrant. Moreover, mutation of the sumoylation targets K266 and K268 within the NLS impaired fulvestrant-induced ERα degradation. In conclusion, our study provides evidence for the unique role of the ERα NLS in fulvestrant-induced degradation of the receptor. © 2015 Elsevier Ireland Ltd.

Registro:

Documento: Artículo
Título:The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor
Autor:Casa, A.J.; Hochbaum, D.; Sreekumar, S.; Oesterreich, S.; Lee, A.V.
Filiación:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, United States
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States
Women's Cancer Research Center, Magee Women's Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, United States
Department of Pharmacology and Chemical Biology, Magee Women's Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, United States
Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, United States
Departamento de Biodiversidad y Biología Experimental, Facultad de Cs. Exactas y Naturales, U.B.A., C1428EHA Ciudad Universitaria Nunez, Ciudad Autónoma de Buenos Aires (CABA), CM2, 2do piso Pabellón 2, Argentina
Palabras clave:Breast cancer; Degradation; Endocrine therapy; Estrogen receptor; Fulvestrant; Nuclear localization sequence; estradiol; estrogen receptor alpha; fulvestrant; estradiol; estrogen receptor alpha; fulvestrant; amino acid sequence; amino terminal sequence; antineoplastic activity; Article; controlled study; drug receptor binding; gene mutation; human; human cell; ligand binding; molecular cloning; priority journal; protein degradation; protein domain; protein function; protein localization; protein processing; protein targeting; sequence analysis; sumoylation; analogs and derivatives; cell nucleus; drug effects; genetics; HEK293 cell line; MCF 7 cell line; metabolism; mutation; protein degradation; Cell Nucleus; Estradiol; Estrogen Receptor alpha; HEK293 Cells; Humans; MCF-7 Cells; Mutation; Proteolysis; Sumoylation
Año:2015
Volumen:415
Página de inicio:76
Página de fin:86
DOI: http://dx.doi.org/10.1016/j.mce.2015.08.007
Título revista:Molecular and Cellular Endocrinology
Título revista abreviado:Mol. Cell. Endocrinol.
ISSN:03037207
CODEN:MCEND
CAS:estradiol, 50-28-2; fulvestrant, 129453-61-8; Estradiol; Estrogen Receptor alpha; fulvestrant
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v415_n_p76_Casa

Referencias:

  • Berry, N.B., Fan, M., Nephew, K.P., Estrogen receptor-alpha hinge-region lysines 302 and 303 regulate receptor degradation by the proteasome (2008) Mol. Endocrinol., 22, pp. 1535-1551
  • Bross, P.F., Cohen, M.H., Williams, G.A., Pazdur, R., FDA drug approval summaries: fulvestrant (2002) Oncology, 7, pp. 477-480
  • Bross, P.F., Baird, A., Chen, G., Jee, J.M., Lostritto, R.T., Morse, D.E., Rosario, L.A., Pazdur, R., Fulvestrant in postmenopausal women with advanced breast cancer (2003) Clin. Cancer Res., 9, pp. 4309-4317
  • Burns, K.A., Li, Y., Arao, Y., Petrovich, R.M., Korach, K.S., Selective mutations in estrogen receptor alpha 's D-domain alters nuclear translocation and non-ERE gene regulatory mechanisms (2011) J. Biol. Chem., 286, pp. 12640-12649
  • Clurman, B.E., Sheaff, R.J., Thress, K., Groudine, M., Roberts, J.M., Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation (1996) Genes Dev., 10, pp. 1979-1990
  • Cui, Y., Zhang, M., Pestell, R., Curran, E.M., Welshons, W.V., Fuqua, S.A., Phosphorylation of estrogen receptor alpha blocks its acetylation and regulates estrogen sensitivity (2004) Cancer Res., 64, pp. 9199-9208
  • Dauvois, S., White, R., Parker, M.G., The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling (1993) J. Cell Sci., 106, pp. 1377-1388
  • DeNardo, D.G., Cuba, V.L., Kim, H., Wu, K., Lee, A.V., Brown, P.H., Estrogen receptor DNA binding is not required for estrogen-induced breast cell growth (2007) Mol. Cell Endocrinol., 277, pp. 13-25
  • Diehl, J.A., Cheng, M., Roussel, M.F., Sherr, C.J., Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization (1998) Genes Dev., 12, pp. 3499-3511
  • Gibson, M.K., Nemmers, L.A., Beckman, W.C., Davis, V.L., Curtis, S.W., Korach, K.S., The mechanism of ICI 164,384 antiestrogenicity involves rapid loss of estrogen receptor in uterine tissue (1991) Endocrinology, 129, pp. 2000-2010
  • Hilmi, K., Hussein, N., Mendoza-Sanchez, R., El-Ezzy, M., Ismail, H., Durette, C., Bail, M., Mader, S., Role of SUMOylation in full antiestrogenicity (2012) Mol. Cell Biol., 32, pp. 3823-3837
  • Jaber, B.M., Gao, T., Huang, L., Karmakar, S., Smith, C.L., The pure estrogen receptor antagonist ICI 182,780 promotes a novel interaction of estrogen receptor-alpha with the 3',5'-cyclic adenosine monophosphate response element-binding protein-binding protein/p300 coactivators (2006) Mol. Endocrinol., 20, pp. 2695-2710
  • Karmakar, S., Gao, T., Pace, M.C., Oesterreich, S., Smith, C.L., Cooperative activation of cyclin D1 and progesterone receptor gene expression by the SRC-3 coactivator and SMRT corepressor (2010) Mol. Endocrinol., 24, pp. 1187-1202
  • Khorasanizadeh, S., Rastinejad, F., Nuclear-receptor interactions on DNA-response elements (2001) Trends Biochem. Sci., 26, pp. 384-390
  • Kocanova, S., Mazaheri, M., Caze-Subra, S., Bystricky, K., Ligands specify estrogen receptor alpha nuclear localization and degradation (2010) BMC Cell Biol., 11, p. 98
  • Lang, I., Scholz, M., Peters, R., Molecular mobility and nucleocytoplasmic flux in hepatoma cells (1986) J. Cell Biol., 102, pp. 1183-1190
  • Li, C., Wu, R.C., Amazit, L., Tsai, S.Y., Tsai, M.J., O'Malley, B.W., Specific amino acid residues in the basic helix-loop-helix domain of SRC-3 are essential for its nuclear localization and proteasome-dependent turnover (2007) Mol. Cell Biol., 27, pp. 1296-1308
  • Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method (2001) Methods, 25, pp. 402-408
  • Lo, R.S., Massague, J., Ubiquitin-dependent degradation of TGF-beta-activated smad2 (1999) Nat. Cell Biol., 1, pp. 472-478
  • Lonard, D.M., Nawaz, Z., Smith, C.L., O'Malley, B.W., The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation (2000) Mol. Cell, 5, pp. 939-948
  • Long, X., Nephew, K.P., Fulvestrant (ICI 182,780)-dependent interacting proteins mediate immobilization and degradation of estrogen receptor-alpha (2006) J. Biol. Chem., 281, pp. 9607-9615
  • Long, X., Fan, M., Nephew, K.P., Estrogen receptor-alpha-interacting cytokeratins potentiate the antiestrogenic activity of fulvestrant (2010) Cancer Biol. Ther., 9, pp. 389-396
  • Marsaud, V., Gougelet, A., Maillard, S., Renoir, J.-M., Various phosphorylation pathways, depending on agonist and antagonist binding to endogenous estrogen receptor α (ERα), differentially affect ERα extractability, proteasome-mediated stability, and transcriptional activity in human breast cancer cells (2003) Mol. Endocrinol., 17, pp. 2013-2027
  • Maynard, P., Davies, C., Blamey, R., Elston, C., Johnson, J., Griffiths, K., Relationship between oestrogen-receptor content and histological grade in human primary breast tumours (1978) Br. J. Cancer, 38, p. 745
  • McGuire, W.L., Current status of estrogen receptors in human breast cancer (1975) Cancer, 36, pp. 638-644
  • Melvin, V.S., Roemer, S.C., Churchill, M.E., Edwards, D.P., The C-terminal extension (CTE) of the nuclear hormone receptor DNA binding domain determines interactions and functional response to the HMGB-1/-2 co-regulatory proteins (2002) J. Biol. Chem., 277, pp. 25115-25124
  • Melvin, V.S., Harrell, C., Adelman, J.S., Kraus, W.L., Churchill, M., Edwards, D.P., The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB (2004) J. Biol. Chem., 279, pp. 14763-14771
  • Molinari, E., Gilman, M., Natesan, S., Proteasome-mediated degradation of transcriptional activators correlates with activation domain potency in vivo (1999) EMBO J., 18, pp. 6439-6447
  • Nawaz, Z., O'Malley, B.W., Urban renewal in the nucleus: is protein turnover by proteasomes absolutely required for nuclear receptor-regulated transcription? (2004) Mol. Endocrinol., 18, pp. 493-499
  • Nawaz, Z., Lonard, D.M., Dennis, A.P., Smith, C.L., O'Malley, B.W., Proteasome-dependent degradation of the human estrogen receptor (1999) Proc. Natl. Acad. Sci. U. S. A., 96, pp. 1858-1862
  • Oesterreich, S., Zhang, Q., Hopp, T., Fuqua, S.A., Michaelis, M., Zhao, H.H., Davie, J.R., Lee, A.V., Tamoxifen-bound estrogen receptor (ER) strongly interacts with the nuclear matrix protein HET/SAF-B, a novel inhibitor of ER-mediated transactivation (2000) Mol. Endocrinol., 14, pp. 369-381
  • Oesterreich, S., Zhang, P., Guler, R.L., Sun, X., Curran, E.M., Welshons, W.V., Osborne, C.K., Lee, A.V., Re-expression of estrogen receptor alpha in estrogen receptor alpha-negative MCF-7 cells restores both estrogen and insulin-like growth factor-mediated signaling and growth (2001) Cancer Res., 61, pp. 5771-5777
  • Osborne, C.K., Wakeling, A., Nicholson, R.I., Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action (2004) Br. J. Cancer, 90, pp. S2-S6
  • Paine, P.L., Moore, L.C., Horowitz, S.B., Nuclear envelope permeability (1975) Nature, 254, pp. 109-114
  • Picard, D., Kumar, V., Chambon, P., Yamamoto, K.R., Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors (1990) Cell Regul., 1, pp. 291-299
  • Roberts, B., Nuclear location signal-mediated protein transport (1989) Biochim. Biophys. Acta, 1008, pp. 263-280
  • Roberts, B.L., Richardson, W.D., Smith, A.E., The effect of protein context on nuclear location signal function (1987) Cell, 50, pp. 465-475
  • Salghetti, S.E., Muratani, M., Wijnen, H., Futcher, B., Tansey, W.P., Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis (2000) Proc. Natl. Acad. Sci. U. S. A., 97, pp. 3118-3123
  • Schultz, J.R., Loven, M.A., Melvin, V.M., Edwards, D.P., Nardulli, A.M., Differential modulation of DNA conformation by estrogen receptors alpha and beta (2002) J. Biol. Chem., 277, pp. 8702-8707
  • Sentis, S., Le Romancer, M., Bianchin, C., Rostan, M.C., Corbo, L., Sumoylation of the estrogen receptor alpha hinge region regulates its transcriptional activity (2005) Mol. Endocrinol., 19, pp. 2671-2684
  • Shang, Y., Myers, M., Brown, M., Formation of the androgen receptor transcription complex (2002) Mol. Cell, 9, pp. 601-610
  • Stenoien, D.L., Mancini, M.G., Patel, K., Allegretto, E.A., Smith, C.L., Mancini, M.A., Subnuclear trafficking of estrogen receptor-alpha and steroid receptor coactivator-1 (2000) Mol. Endocrinol., 14, pp. 518-534
  • Stenoien, D.L., Patel, K., Mancini, M.G., Dutertre, M., Smith, C.L., O'Malley, B.W., Mancini, M.A., FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent (2001) Nat. Cell Biol., 3, pp. 15-23
  • Valley, C.C., Metivier, R., Solodin, N.M., Fowler, A.M., Mashek, M.T., Hill, L., Alarid, E.T., Differential regulation of estrogen-inducible proteolysis and transcription by the estrogen receptor alpha N terminus (2005) Mol. Cell Biol., 25, pp. 5417-5428
  • Wang, C., Fu, M., Angeletti, R.H., Siconolfi-Baez, L., Reutens, A.T., Albanese, C., Lisanti, M.P., Pestell, R.G., Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity (2001) J. Biol. Chem., 276, pp. 18375-18383
  • Welcker, M., Singer, J., Loeb, K.R., Grim, J., Bloecher, A., Gurien-West, M., Clurman, B.E., Roberts, J.M., Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation (2003) Mol. Cell, 12, pp. 381-392
  • Wijayaratne, A.L., McDonnell, D.P., The human estrogen receptor-alpha is a ubiquitinated protein whose stability is affected differentially by agonists, antagonists, and selective estrogen receptor modulators (2001) J. Biol. Chem., 276, pp. 35684-35692
  • Won, K.A., Reed, S.I., Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E (1996) EMBO J., 15, pp. 4182-4193
  • Ylikomi, T., Bocquel, M.T., Berry, M., Gronemeyer, H., Chambon, P., Cooperation of proto-signals for nuclear accumulation of estrogen and progesterone receptors (1992) EMBO J., 11, pp. 3681-3694
  • Zhou, Q., Shaw, P.G., Davidson, N.E., Epigenetics meets estrogen receptor: regulation of estrogen receptor by direct lysine methylation (2009) Endocr. Relat. Cancer, 16, pp. 319-323

Citas:

---------- APA ----------
Casa, A.J., Hochbaum, D., Sreekumar, S., Oesterreich, S. & Lee, A.V. (2015) . The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor. Molecular and Cellular Endocrinology, 415, 76-86.
http://dx.doi.org/10.1016/j.mce.2015.08.007
---------- CHICAGO ----------
Casa, A.J., Hochbaum, D., Sreekumar, S., Oesterreich, S., Lee, A.V. "The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor" . Molecular and Cellular Endocrinology 415 (2015) : 76-86.
http://dx.doi.org/10.1016/j.mce.2015.08.007
---------- MLA ----------
Casa, A.J., Hochbaum, D., Sreekumar, S., Oesterreich, S., Lee, A.V. "The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor" . Molecular and Cellular Endocrinology, vol. 415, 2015, pp. 76-86.
http://dx.doi.org/10.1016/j.mce.2015.08.007
---------- VANCOUVER ----------
Casa, A.J., Hochbaum, D., Sreekumar, S., Oesterreich, S., Lee, A.V. The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor. Mol. Cell. Endocrinol. 2015;415:76-86.
http://dx.doi.org/10.1016/j.mce.2015.08.007