This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nair, S. S. Articles by Vadlamudi, R. K. Search for Related Content PubMed PubMed Citation Articles by Nair, S. S. Articles by Vadlamudi, R. K.

Potential Role of a Novel Transcriptional Coactivator PELP1 in Histone H1 Displacement in Cancer Cells

Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

The estrogen receptor plays an important role in breast cancer progression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), also called modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptor, modulates estrogen receptor transactivation functions. The mechanisms by which PELP1 modulates estrogen receptor genomic functions is not known. Here, using biochemical and scanning confocal microscopic analysis, we have demonstrated nuclear localization and functional implications of PELP1. Subnuclear fractionation showed PELP1 association with chromatin and nuclear matrix fractions. Ligand stimulation promoted recruitment of PELP1 to 17ß-estradiol responsive promoters, its colocalization with acetylated H3, and increased PELP1-associated histone acetyltransferase enzymatic activity. Far Western analysis revealed that PELP1 interacts with histone 1 and 3, with more preference toward histone 1. Using deletion analysis, we have identified the PELP1 COOH-terminal region as the histone 1 binding site. The PELP1 mutant lacking histone 1-binding domain acts as a dominant-negative and blocks estrogen receptor -mediated transcription. Chromatin immunoprecipitation analysis showed a cyclic association and dissociation of PELP1 with the promoter, with recruitment of histone 1 and PELP1 occurring in opposite phases. PELP1 overexpression increased the micrococcal nuclease sensitivity of estrogen response element-containing nucleosomes. Our results provide novel insights about the transcription regulation of PELP1 and suggest that PELP1 participates in chromatin remodeling activity via displacement of histone 1 in cancer cells.

This article has been cited by other articles:

				C. Dimple, S. S. Nair, R. Rajhans, P. R. Pitcheswara, J. Liu, S. Balasenthil, X.-F. Le, M. E. Burow, N. Auersperg, R. R. Tekmal, et al. Role of PELP1/MNAR Signaling in Ovarian Tumorigenesis Cancer Res., June 15, 2008; 68(12): 4902 - 4909. [Abstract] [Full Text] [PDF]

				J. K. Nagpal, S. Nair, D. Chakravarty, R. Rajhans, S. Pothana, D. W. Brann, R. R. Tekmal, and R. K. Vadlamudi Growth Factor Regulation of Estrogen Receptor Coregulator PELP1 Functions via Protein Kinase A Pathway Mol. Cancer Res., May 1, 2008; 6(5): 851 - 861. [Abstract] [Full Text] [PDF]

				R. Rajhans, H. B. Nair, S. S. Nair, V. Cortez, K. Ikuko, N. B. Kirma, D. Zhou, A. E. Holden, D. W Brann, S. Chen, et al. Modulation of in Situ Estrogen Synthesis by Proline-, Glutamic Acid-, and Leucine-Rich Protein-1: Potential Estrogen Receptor Autocrine Signaling Loop in Breast Cancer Cells Mol. Endocrinol., March 1, 2008; 22(3): 649 - 664. [Abstract] [Full Text] [PDF]

				A. E. Gururaj, S. Peng, R. K. Vadlamudi, and R. Kumar Estrogen Induces Expression of BCAS3, a Novel Estrogen Receptor-{alpha} Coactivator, through Proline-, Glutamic Acid-, and Leucine-Rich Protein-1 (PELP1) Mol. Endocrinol., August 1, 2007; 21(8): 1847 - 1860. [Abstract] [Full Text] [PDF]

				R. Rajhans, S. Nair, A. H. Holden, R. Kumar, R. R. Tekmal, and R. K. Vadlamudi Oncogenic Potential of the Nuclear Receptor Coregulator Proline-, Glutamic Acid-, Leucine-Rich Protein 1/Modulator of the Nongenomic Actions of the Estrogen Receptor Cancer Res., June 1, 2007; 67(11): 5505 - 5512. [Abstract] [Full Text] [PDF]

				S. S. Nair, Z. Guo, J. M. Mueller, S. Koochekpour, Y. Qiu, R. R. Tekmal, R. Schule, H.-J. Kung, R. Kumar, and R. K. Vadlamudi Proline-, Glutamic Acid-, and Leucine-Rich Protein-1/Modulator of Nongenomic Activity of Estrogen Receptor Enhances Androgen Receptor Functions through LIM-Only Coactivator, Four-and-a-Half LIM-Only Protein 2 Mol. Endocrinol., March 1, 2007; 21(3): 613 - 624. [Abstract] [Full Text] [PDF]

				P. den Hollander, S. K. Rayala, D. Coverley, and R. Kumar Ciz1, a Novel DNA-Binding Coactivator of the Estrogen Receptor {alpha}, Confers Hypersensitivity to Estrogen Action. Cancer Res., November 15, 2006; 66(22): 11021 - 11029. [Abstract] [Full Text] [PDF]

				K. Ohshiro, S. K. Rayala, M. D. Williams, R. Kumar, and A. K. El-Naggar Biological Role of Estrogen Receptor {beta} in Salivary Gland Adenocarcinoma Cells. Clin. Cancer Res., October 15, 2006; 12(20): 5994 - 5999. [Abstract] [Full Text] [PDF]

				S. K. Rayala, P. den Hollander, B. Manavathi, A. H. Talukder, C. Song, S. Peng, A. Barnekow, J. Kremerskothen, and R. Kumar Essential Role of KIBRA in Co-activator Function of Dynein Light Chain 1 in Mammalian Cells J. Biol. Chem., July 14, 2006; 281(28): 19092 - 19099. [Abstract] [Full Text] [PDF]

				A. Rosendorff, S. Sakakibara, S. Lu, E. Kieff, Y. Xuan, A. DiBacco, Y. Shi, Y. Shi, and G. Gill NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression PNAS, April 4, 2006; 103(14): 5308 - 5313. [Abstract] [Full Text] [PDF]

				S. K. Rayala, P. d. Hollander, S. Balasenthil, P. R. Molli, A. J. Bean, R. K. Vadlamudi, R.-A. Wang, and R. Kumar Hepatocyte Growth Factor-regulated Tyrosine Kinase Substrate (HRS) Interacts with PELP1 and Activates MAPK J. Biol. Chem., February 17, 2006; 281(7): 4395 - 4403. [Abstract] [Full Text] [PDF]

				S. K. Rayala, J. Mascarenhas, R. K. Vadlamudi, and R. Kumar Altered localization of a coactivator sensitizes breast cancer cells to tumor necrosis factor-induced apoptosis. Mol. Cancer Ther., February 1, 2006; 5(2): 230 - 237. [Abstract] [Full Text] [PDF]

				A. E. Gururaj, S. K. Rayala, R. K. Vadlamudi, and R. Kumar Novel Mechanisms of Resistance to Endocrine Therapy: Genomic and Nongenomic Considerations Clin. Cancer Res., February 1, 2006; 12(3): 1001s - 1007s. [Abstract] [Full Text] [PDF]

				R. K. Vadlamudi, B. Manavathi, S. Balasenthil, S. S. Nair, Z. Yang, A. A. Sahin, and R. Kumar Functional Implications of Altered Subcellular Localization of PELP1 in Breast Cancer Cells Cancer Res., September 1, 2005; 65(17): 7724 - 7732. [Abstract] [Full Text] [PDF]

				B. Manavathi, S. S. Nair, R.-A. Wang, R. Kumar, and R. K. Vadlamudi Proline-, Glutamic Acid-, and Leucine-Rich Protein-1 Is Essential in Growth Factor Regulation of Signal Transducers and Activators of Transcription 3 Activation Cancer Res., July 1, 2005; 65(13): 5571 - 5577. [Abstract] [Full Text] [PDF]

				R. K. Vadlamudi, S. Balasenthil, R. R. Broaddus, J.-A. Gustafsson, and R. Kumar Deregulation of Estrogen Receptor Coactivator Proline-, Glutamic Acid-, and Leucine-Rich Protein-1/Modulator of Nongenomic Activity of Estrogen Receptor in Human Endometrial Tumors J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6130 - 6138. [Abstract] [Full Text] [PDF]