Coleman KM, Lam V, Jaber BM, Lanz RB, Smith CL ^@

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030-3498, USA.

^@ Corresponding author. Fax: +1 713 790 1275
E-mail:  carolyns@bcm.tmc.edu

The ability of steroid receptor RNA activator (SRA), an AF-1 coactivator, to contribute to differences in estrogen receptor (ER)-alpha and ERbeta transcriptional activity was tested. In transient transfections, SRA expression increased ERalpha- and ERbeta-dependent gene expression. However, when the receptors' amino-terminal A/B regions were examined as GAL4 DNA binding domain fusions, SRA enhanced the activity of GAL-ABalpha but not GAL-ABbeta. Exogenous SRA also enhanced AF-2 activity for both receptors, indicating that SRA effects are not limited to AF-1. Simultaneously mutating three phosphorylation sites within GAL-ABalpha domain only modestly reduced SRA coactivation of GAL-ABalpha, suggesting that phosphorylation does not play a major role in SRA function relative to this domain. SRA enhanced ERalpha activity stimulated by 4-hydroxytamoxifen, but was unable to convert this mixed antiestrogen to an ERbeta agonist. Thus, SRA is an ERalpha AF-1-specific coactivator that enhances the agonist activity of tamoxifen-bound ERalpha and may contribute to tamoxifen resistance. 

A Brief History of Activator RNA:
 

Additional References:

1. Lanz RB, Chua SS, Barron N, Söder BM, DeMayo F, and O'Malley BW, "Steroid Receptor RNA Activator Stimulates Proliferation as Well as Apoptosis In Vivo", Molecular and Cellular Biology, vol. 23, no. 20, pp. 7163-7176 (October, 2003).

2. Lanz RB, Razani B, Goldberg AD, and O'Malley BW, "Distinct RNA Motifs are Important for Coactivation of Steroid Hormone Receptors by Steroid Receptor RNA Activator (SRA)", Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 25, 16081-16086, December 10, 2002.

3. Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, and O'Malley BW, "A Steroid Receptor Coactivator, SRA, Functions as an RNA and is Present in an SRC-1 Complex", Cell, vol. 97, no.1, pp. 17-27 (April 2, 1999).

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Additional References:

Links to RNA and Biological Causality:

Links to Euchromatin Activator RNA Research:

A Brief History of Activator RNA:

Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:
Links to Selective Gene Transcription:
Links to RNA-Induced Epigenetics:
Links to RNA-Induced Embryogenesis:
Links to RNA and Biological Causality:
Links to Reprogramming and Neoplasia:

A Brief History of Activator RNA:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".

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