A model for hormone receptor binding to the mouse mammary tumour virus regulatory element bared on hydroxyl radical footprinting

Chalepakis, Georges; Postma, Jochen P. M.; Beato, Miguel

doi:10.1093/nar/16.21.10237

Cited by 34 publications

(15 citation statements)

References 20 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Luciferase reporter vectors were tested that contain enhancer/promoter regions from the androgen-regulated genes, PSA (16,17), probasin (18), sex-limited protein (pGC⌬9) (19,20), and MMTV (21)(22)(23). The role of the WXXLF and FXXLF motifs and effects of TIF2 coactivation on luciferase activity were determined using wild-type AR (AR-FXXLF/ WXXLF) or AR in which FXXLF was changed to FXXAA, WXXLF was changed to AXXAA, or both mutations were created in the same protein.…”

Section: Resultsmentioning

confidence: 99%

“…In our studies, the MMTV, PSA, and probasin luciferase reporters were activated by AR and GR, whereas there was little GR transactivation of pGL⌬9. It is well established that GR stimulates the MMTV promoter (21)(22)(23), whereas the probasin (34,35) and pGL⌬9 (20) enhancer/promoters are reported to be selectively activated by AR. It was the PSA, probasin and pGL⌬9 enhancer/promoters that showed increased transactivation by the GR chimera with an imposed N/C interaction.…”

Section: Tif2 Coactivation Of Ar-mediated Transactivation Of the Psa mentioning

confidence: 99%

See 1 more Smart Citation

Dependence of Selective Gene Activation on the Androgen Receptor NH2- and COOH-terminal Interaction

Lee

Minges

et al. 2002

Journal of Biological Chemistry

146

143

View full text Add to dashboard Cite

The agonist-induced androgen receptor NH 2 -and COOH-terminal (N/C) interaction is mediated by the FXXLF and WXXLF NH 2 -terminal motifs. Here we demonstrate that agonist-dependent transactivation of prostate-specific antigen (PSA) and probasin enhancer/promoter regions requires the N/C interaction, whereas the sex-limited protein gene and mouse mammary tumor virus long terminal repeat do not. Transactivation of PSA and probasin response regions also depends on activation function 1 (AF1) in the NH 2 -terminal region but can be increased by binding an overexpressed p160 coactivator to activation function 2 (AF2) in the ligand binding domain. The dependence of the PSA and probasin enhancer/promoters on the N/C interaction for transactivation allowed us to demonstrate that in the presence of androgen, the WXXLF motif with the sequence 433 WHTLF 437 contributes as an inhibitor to AR transactivation. We further show that like the FXXLF and LXXLL motifs, the WXXLF motif interacts in the presence of androgen with AF2 in the ligand binding domain. Sequence comparisons among species indicate greater conservation of the FXXLF motif compared with the WXXLF motif, paralleling the functional significance of these binding motifs. The data provide evidence for promoter-specific differences in the requirement for the androgen receptor N/C interaction and in the contributions of AF1 and AF2 in androgen-induced gene regulation.Steroid receptors are ligand-activated transcription factors that regulate gene activation through a series of events triggered by high affinity hormone binding and mediated by receptor binding to response element DNA and coactivators. At least two domains have been identified that mediate nuclear receptor interactions with coregulators. These are activation function 1 (AF1) 1 in the NH 2 -terminal region and activation function 2 (AF2) in the ligand binding domain. The AF2 binding surface in the ligand binding domain is comprised of helices 3, 4, and 12 and forms after hormone binding. For many nuclear receptors, transactivation depends on AF2 recruitment of p160 coactivator complexes that have histone acetyl transferase activity to modify chromatin structure (1). The p160 coactivators are a group of proteins that include steroid receptor coactivator 1 (SRC1), transcriptional intermediary protein 2 (TIF2, GRIP1 or SRC2), and the steroid receptor coactivator 3 subfamily (SRC3). Interaction with AF2 is mediated by the p160 coactivator LXXLL motif that forms an amphipathic ␣-helix and binds the AF2 hydrophobic binding surface in the nuclear receptor ligand binding domain (2-5). For the androgen receptor (AR), the functional importance of AF2 recruitment of p160 coactivators is unclear, with data implicating the AR NH 2 -terminal AF1 region in AR-mediated gene activation. The AF2 binding site in the AR ligand binding domain was shown to mediate the agonist-induced NH 2 -and COOH-terminal (N/C) interaction (6 -10). Agonist-induced N/C interdomain interactions are also reported for the estrogen (11) and progest...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Tif2 Coactivation Of Ar-mediated Transactivation Of the Psa mentioning

confidence: 99%

Dependence of Selective Gene Activation on the Androgen Receptor NH2- and COOH-terminal Interaction

Lee

Minges

et al. 2002

Journal of Biological Chemistry

146

143

View full text Add to dashboard Cite

show abstract

“…MMTV first came to prominence when it was shown to cause breast cancer in mice [8][9][10][11][12][13][14]. Since then, MMTV-LV sequences have been identified in approximately 40% of human breast cancers [15][16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Mouse mammary tumour virus-like virus (MMTV-LV) is present within the liver in a wide range of hepatic disorders and unrelated to nuclear p53 expression or hepatocarcinogenesis

Johal

Scott

Jones

et al. 2009

Journal of Hepatology

View full text Add to dashboard Cite

“…In the present study the progesterone receptors could be localized in the nuclei of the subdural mesothelial cells lining the arachnoid cyst. The receptor molecule possesses a so-called DNA response element, a domain containing two so-called zinc-fingers which can interact with the hormone regulatory element of the DNA molecule, where the interaction elicits transcription of the hormone dependent gene [4,27]. After binding the steroid ligand, the receptor-ligand complex has been shown to move into the nucleus, in which it is assumed to interact with the nuclear DNA [13].…”

Section: Discussionmentioning

confidence: 99%

Progesterone receptors in arachnoid cysts

Kito

Blankenstein

Vroom³

et al. 1997

Acta neurochir

View full text Add to dashboard Cite

We report 2 cases of arachnoid cysts, one with a retrocerebellar and the other with a left temporal localization, in which immunohistochemical studies had been conducted. The results of the immunohistochemistry on the presence of carcino-embryonic antigen (CEA) and glial fibrillary acidic protein (GFAP), and of the scanning- and transmission electron microscopy revealed the cyst lining to be identical to subdural neurothelium. Progesterone receptors were found in the nuclei of cells lining the cyst, which also suggests the similarity of the cyst lining to arachnoid granulations and meningiomas as derivatives of subdural neurothelium, which also possess progesterone receptors.

show abstract

A model for hormone receptor binding to the mouse mammary tumour virus regulatory element bared on hydroxyl radical footprinting

Cited by 34 publications

References 20 publications

Dependence of Selective Gene Activation on the Androgen Receptor NH2- and COOH-terminal Interaction

Dependence of Selective Gene Activation on the Androgen Receptor NH2- and COOH-terminal Interaction

Mouse mammary tumour virus-like virus (MMTV-LV) is present within the liver in a wide range of hepatic disorders and unrelated to nuclear p53 expression or hepatocarcinogenesis

Progesterone receptors in arachnoid cysts

Contact Info

Product

Resources

About