The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor transactivation functions - PubMed (original) (raw)
The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor transactivation functions
P Webb et al. Mol Endocrinol. 1999 Oct.
Abstract
Estrogen receptors (ERs alpha and beta) enhance transcription in response to estrogens by binding to estrogen response elements (EREs) within target genes and utilizing transactivation functions (AF-1 and AF-2) to recruit p160 coactivator proteins. The ERs also enhance transcription in response to estrogens and antiestrogens by modulating the activity of the AP-1 protein complex. Here, we examine the role of AF-1 and AF-2 in ER action at AP-1 sites. Estrogen responses at AP-1 sites require the integrity of the ERalpha AF-1 and AF-2 activation surfaces and the complementary surfaces on the p160 coactivator GRIP1 (glucocorticoid receptor interacting protein 1), the NID/AF-1 region, and NR boxes. Thus, estrogen-liganded ERalpha utilizes the same protein-protein contacts to transactivate at EREs and AP-1 sites. In contrast, antiestrogen responses are strongly inhibited by ERalpha AF-1 and weakly inhibited by AF-2. Indeed, ERalpha truncations that lack AF-1 enhance AP-1 activity in the presence of antiestrogens, but not estrogens. This phenotype resembles ERbeta, which naturally lacks constitutive AF-1 activity. We conclude that the ERs enhance AP-1 responsive transcription by distinct mechanisms with different requirements for ER transactivation functions. We suggest that estrogen-liganded ER enhances AP-1 activity via interactions with p160s and speculate that antiestrogen-liganded ER enhances AP-1 activity via interactions with corepressors.
Similar articles
- Estrogen receptor activation function 1 works by binding p160 coactivator proteins.
Webb P, Nguyen P, Shinsako J, Anderson C, Feng W, Nguyen MP, Chen D, Huang SM, Subramanian S, McKinerney E, Katzenellenbogen BS, Stallcup MR, Kushner PJ. Webb P, et al. Mol Endocrinol. 1998 Oct;12(10):1605-18. doi: 10.1210/mend.12.10.0185. Mol Endocrinol. 1998. PMID: 9773983 - Estradiol repression of tumor necrosis factor-alpha transcription requires estrogen receptor activation function-2 and is enhanced by coactivators.
An J, Ribeiro RC, Webb P, Gustafsson JA, Kushner PJ, Baxter JD, Leitman DC. An J, et al. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15161-6. doi: 10.1073/pnas.96.26.15161. Proc Natl Acad Sci U S A. 1999. PMID: 10611355 Free PMC article. - Suppression by estrogen receptor beta of AP-1 mediated transactivation through estrogen receptor alpha.
Maruyama S, Fujimoto N, Asano K, Ito A. Maruyama S, et al. J Steroid Biochem Mol Biol. 2001 Aug;78(2):177-84. doi: 10.1016/s0960-0760(01)00083-8. J Steroid Biochem Mol Biol. 2001. PMID: 11566442 - Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology.
Katzenellenbogen BS, Choi I, Delage-Mourroux R, Ediger TR, Martini PG, Montano M, Sun J, Weis K, Katzenellenbogen JA. Katzenellenbogen BS, et al. J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):279-85. doi: 10.1016/s0960-0760(00)00104-7. J Steroid Biochem Mol Biol. 2000. PMID: 11162936 Review. - Estrogen receptor pathways to AP-1.
Kushner PJ, Agard DA, Greene GL, Scanlan TS, Shiau AK, Uht RM, Webb P. Kushner PJ, et al. J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):311-7. doi: 10.1016/s0960-0760(00)00108-4. J Steroid Biochem Mol Biol. 2000. PMID: 11162939 Review.
Cited by
- Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.
Dias Da Silva I, Wuidar V, Zielonka M, Pequeux C. Dias Da Silva I, et al. Cells. 2024 Jul 23;13(15):1236. doi: 10.3390/cells13151236. Cells. 2024. PMID: 39120268 Free PMC article. Review. - ESR1 fusions and therapeutic resistance in metastatic breast cancer.
Nagy Z, Jeselsohn R. Nagy Z, et al. Front Oncol. 2023 Jan 4;12:1037531. doi: 10.3389/fonc.2022.1037531. eCollection 2022. Front Oncol. 2023. PMID: 36686845 Free PMC article. Review. - Estrogen Receptor Alpha and ESR1 Mutations in Breast Cancer.
Patel JM, Jeselsohn RM. Patel JM, et al. Adv Exp Med Biol. 2022;1390:171-194. doi: 10.1007/978-3-031-11836-4_10. Adv Exp Med Biol. 2022. PMID: 36107319 - Like Brothers in Arms: How Hormonal Stimuli and Changes in the Metabolism Signaling Cooperate, Leading HPV Infection to Drive the Onset of Cervical Cancer.
Läsche M, Gallwas J, Gründker C. Läsche M, et al. Int J Mol Sci. 2022 May 2;23(9):5050. doi: 10.3390/ijms23095050. Int J Mol Sci. 2022. PMID: 35563441 Free PMC article. Review. - Estrogen Biosynthesis and Signal Transduction in Ovarian Disease.
Xu XL, Huang ZY, Yu K, Li J, Fu XW, Deng SL. Xu XL, et al. Front Endocrinol (Lausanne). 2022 Mar 1;13:827032. doi: 10.3389/fendo.2022.827032. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 35299973 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous