Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Mol. Cell. Biol. 22 (18): 6611-6626

Copyright © 2002 by the American Society for Microbiology. All rights reserved.

Microtubule-Dependent Subcellular Redistribution of the Transcriptional Coactivator p/CIP

Majdi S. Qutob,1,2,3 Rabindra N. Bhattacharjee,1,2,4 Elisa Pollari,1,2,4 Siu Pok Yee,1,2,3 and Joseph Torchia1,2,4*

Cancer Research Laboratories, London Regional Cancer Centre,1 Departments of Oncology,2 Biochemistryand,3 Pharmacology and Toxicology, The University of Western Ontario, London, Ontario, Canada4

Received for publication 27 November 2001. Revision received 15 January 2002. Accepted for publication 6 June 2002.

Abstract: The transcriptional coactivator p/CIP is a member of a family of nuclear receptor coactivator/steroid receptor coactivator (NCoA/SRC) proteins that mediate the transcriptional activities of nuclear hormone receptors. We have found that p/CIP is predominantly cytoplasmic in a large proportion of cells in various tissues of the developing mouse and in a number of established cell lines. In mouse embryonic fibroblasts, serum deprivation results in the redistribution of p/CIP to the cytoplasmic compartment and stimulation with growth factors or tumor-promoting phorbol esters promotes p/CIP shuttling into the nucleus. Cytoplasmic accumulation of p/CIP is also cell cycle dependent, occurring predominantly during the S and late M phases. Leptomycin B (LMB) treatment results in a marked nuclear accumulation, suggesting that p/CIP undergoes dynamic nuclear export as well as import. We have identified a strong nuclear import signal in the N terminus of p/CIP and two leucine-rich motifs in the C terminus that resemble CRM-1-dependent nuclear export sequences. When fused to green fluorescent protein, the nuclear export sequence region is cytoplasmic and is retained in the nucleus in an LMB-dependent manner. Disruption of the leucine-rich motifs prevents cytoplasmic accumulation. Furthermore, we demonstrate that cytoplasmic p/CIP associates with tubulin and that an intact microtubule network is required for intracellular shuttling of p/CIP. Immunoaffinity purification of p/CIP from nuclear and cytosolic extracts revealed that only nuclear p/CIP complexes possess histone acetyltransferase activity. Collectively, these results suggest that cellular compartmentalization of NCoA/SRC proteins could potentially regulate nuclear hormone receptor-mediated events as well as integrating signals in response to different environmental cues.

* Corresponding author. Mailing address: Cancer Research Laboratories, London Regional Cancer Center, London, Ontario, Canada, N6A 4L6. Phone: (519) 685-8692. Fax: (519) 685-8673. E-mail: jtorchia{at}uwo.ca.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Role of the Nuclear Receptor Coactivator AIB1-{Delta}4 Splice Variant in the Control of Gene Transcription.
C. D. Chien, A. Kirilyuk, J. V. Li, W. Zhang, T. Lahusen, M. O. Schmidt, A. S. Oh, A. Wellstein, and A. T. Riegel (2011)
J. Biol. Chem. 286, 26813-26827
   Abstract »    Full Text »    PDF »
Tyrosine Phosphorylation of the Nuclear Receptor Coactivator AIB1/SRC-3 Is Enhanced by Abl Kinase and Is Required for Its Activity in Cancer Cells.
A. S. Oh, J. T. Lahusen, C. D. Chien, M. P. Fereshteh, X. Zhang, S. Dakshanamurthy, J. Xu, B. L. Kagan, A. Wellstein, and A. T. Riegel (2008)
Mol. Cell. Biol. 28, 6580-6593
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase/AKT Signaling Can Promote AIB1 Stability Independently of GSK3 Phosphorylation.
M. Ferrero, A. Avivar, M. C. Garcia-Macias, and J. F. de Mora (2008)
Cancer Res. 68, 5450-5459
   Abstract »    Full Text »    PDF »
Regulation of SRC-3 Intercompartmental Dynamics by Estrogen Receptor and Phosphorylation.
L. Amazit, L. Pasini, A. T. Szafran, V. Berno, R.-C. Wu, M. Mielke, E. D. Jones, M. G. Mancini, C. A. Hinojos, B. W. O'Malley, et al. (2007)
Mol. Cell. Biol. 27, 6913-6932
   Abstract »    Full Text »    PDF »
Steroid receptor coactivator 3 is a coactivator for myocardin, the regulator of smooth muscle transcription and differentiation.
H. J. Li, Z. Haque, Q. Lu, L. Li, R. Karas, and M. Mendelsohn (2007)
PNAS 104, 4065-4070
   Abstract »    Full Text »    PDF »
Specific Amino Acid Residues in the Basic Helix-Loop-Helix Domain of SRC-3 Are Essential for Its Nuclear Localization and Proteasome-Dependent Turnover.
C. Li, R.-C. Wu, L. Amazit, S. Y. Tsai, M.-J. Tsai, and B. W. O'Malley (2007)
Mol. Cell. Biol. 27, 1296-1308
   Abstract »    Full Text »    PDF »
The Activity and Stability of the Transcriptional Coactivator p/CIP/SRC-3 Are Regulated by CARM1-Dependent Methylation.
H. Naeem, D. Cheng, Q. Zhao, C. Underhill, M. Tini, M. T. Bedford, and J. Torchia (2007)
Mol. Cell. Biol. 27, 120-134
   Abstract »    Full Text »    PDF »
E6AP Mediates Regulated Proteasomal Degradation of the Nuclear Receptor Coactivator Amplified in Breast Cancer 1 in Immortalized Cells..
A. Mani, A. S. Oh, E. T. Bowden, T. Lahusen, K. L. Lorick, A. M. Weissman, R. Schlegel, A. Wellstein, and A. T. Riegel (2006)
Cancer Res. 66, 8680-8686
   Abstract »    Full Text »    PDF »
Steroid Receptor Coactivator-3 Is Required for Progesterone Receptor Trans-activation of Target Genes in Response to Gonadotropin-releasing Hormone Treatment of Pituitary Cells.
B.-S. An, D. M. Selva, G. L. Hammond, A. Rivero-Muller, N. Rahman, and P. C. K. Leung (2006)
J. Biol. Chem. 281, 20817-20824
   Abstract »    Full Text »    PDF »
Differential Recruitment of p160 Coactivators by Glucocorticoid Receptor between Schwann Cells and Astrocytes.
J. Grenier, A. Trousson, A. Chauchereau, J. Cartaud, M. Schumacher, and C. Massaad (2006)
Mol. Endocrinol. 20, 254-267
   Abstract »    Full Text »    PDF »
Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis.
J. Igarashi-Migitaka, A. Takeshita, N. Koibuchi, S. Yamada, R. Ohtani-Kaneko, and K. Hirata (2005)
Eur. J. Endocrinol. 153, 595-604
   Abstract »    Full Text »    PDF »
Rapid Estrogen-Induced Phosphorylation of the SRC-3 Coactivator Occurs in an Extranuclear Complex Containing Estrogen Receptor.
F. F. Zheng, R.-C. Wu, C. L. Smith, and B. W. O'Malley (2005)
Mol. Cell. Biol. 25, 8273-8284
   Abstract »    Full Text »    PDF »
Activation of the Steroid and Xenobiotic Receptor (Human Pregnane X Receptor) by Nontaxane Microtubule-Stabilizing Agents.
S. Mani, H. Huang, S. Sundarababu, W. Liu, G. Kalpana, A. B. Smith, and S. B. Horwitz (2005)
Clin. Cancer Res. 11, 6359-6369
   Abstract »    Full Text »    PDF »
Regulating Inducible Transcription Through Controlled Localization.
E. C. Ziegler and S. Ghosh (2005)
Sci. STKE 2005, re6
   Abstract »    Full Text »    PDF »
Selective Recruitment of p160 Coactivators on Glucocorticoid-Regulated Promoters in Schwann Cells.
J. Grenier, A. Trousson, A. Chauchereau, L. Amazit, A. Lamirand, P. Leclerc, A. Guiochon-Mantel, M. Schumacher, and C. Massaad (2004)
Mol. Endocrinol. 18, 2866-2879
   Abstract »    Full Text »    PDF »
Large-scale Identification of Tubulin-binding Proteins Provides Insight on Subcellular Trafficking, Metabolic Channeling, and Signaling in Plant Cells.
S. D. X. Chuong, A. G. Good, G. J. Taylor, M. C. Freeman, G. B. G. Moorhead, and D. G. Muench (2004)
Mol. Cell. Proteomics 3, 970-983
   Abstract »    Full Text »    PDF »
Overexpression of the Nuclear Receptor Coactivator AIB1 (SRC-3) during Progression of Pancreatic Adenocarcinoma.
R. T. Henke, B. R. Haddad, S. E. Kim, J. D. Rone, A. Mani, J. M. Jessup, A. Wellstein, A. Maitra, and A. T. Riegel (2004)
Clin. Cancer Res. 10, 6134-6142
   Abstract »    Full Text »    PDF »
Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators.
C. L. Smith and B. W. O'Malley (2004)
Endocr. Rev. 25, 45-71
   Abstract »    Full Text »    PDF »
rigor mortis encodes a novel nuclear receptor interacting protein required for ecdysone signaling during Drosophila larval development.
J. Gates, G. Lam, J. A. Ortiz, R. Losson, and C. S. Thummel (2004)
Development 131, 25-36
   Abstract »    Full Text »    PDF »
The T-box Factor Tpit Recruits SRC/p160 Co-activators and Mediates Hormone Action.
M. Maira, C. Couture, G. Le Martelot, A.-M. Pulichino, S. Bilodeau, and J. Drouin (2003)
J. Biol. Chem. 278, 46523-46532
   Abstract »    Full Text »    PDF »
Subcellular Localization and Mechanisms of Nucleocytoplasmic Trafficking of Steroid Receptor Coactivator-1.
L. Amazit, Y. Alj, R. K. Tyagi, A. Chauchereau, H. Loosfelt, C. Pichon, J. Pantel, E. Foulon-Guinchard, P. Leclerc, E. Milgrom, et al. (2003)
J. Biol. Chem. 278, 32195-32203
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882