A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor).

Saatcioglu, Fahri; Bartůněk, Petr; Deng, Tiliang; Zenke, Martin; Karin, Michael

doi:10.1128/mcb.13.6.3675

Cited by 102 publications

(101 citation statements)

References 62 publications

(65 reference statements)

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“…Plasmids with mutated forms of TR␣ and RXR␣ have been described previously (21,22). RAP250 deletion constructs were made by PCR and subcloned into the NotI/NheI sites of the plasmid pSG5Gal4(GBT9J).…”

Section: Methodsmentioning

confidence: 99%

“…These plasmids were used both for transient transfection experiments and/or to in vitro translate RAP250 partial fragments. The following eukaryotic expression vectors were used to express NRs: pSG5mPPAR␥2, pSG5-cTR␣ (22), and pCMX-rRXR␣ (21). pVP16-mRAP250 (aa 782-1138) was made by subcloning an EcoRI fragment from pGAD10-mRAP250 into pCMV-VP16.…”

Section: Methodsmentioning

confidence: 99%

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Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator

Caira¹,

Antonson²,

Pelto‐Huikko³

et al. 2000

Journal of Biological Chemistry

127

112

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Ligand-induced transcriptional activation of gene expression by nuclear receptors is dependent on recruitment of coactivators as intermediary factors. The present work describes the cloning and characterization of RAP250, a novel human nuclear receptor coactivator. The results of in vitro and in vivo experiments indicate that the interaction of RAP250 with nuclear receptors is ligand-dependent or ligand-enhanced depending on the nuclear receptor and involves only one short LXXLL motif called nuclear receptor box. Transient transfection assays further demonstrate that RAP250 has a large intrinsic glutamine-rich activation domain and can significantly enhance the transcriptional activity of several nuclear receptors, acting as a coactivator. Interestingly, Northern blot and in situ hybridization analyses reveal that RAP250 is widely expressed with the highest expression in reproductive organs (testis, prostate and ovary) and brain. Together, our data suggest that RAP250 may play an important role in mammalian gene expression mediated by nuclear receptor.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator

Caira¹,

Antonson²,

Pelto‐Huikko³

et al. 2000

Journal of Biological Chemistry

127

112

View full text Add to dashboard Cite

show abstract

“…Although it fails to repress AP-1 activity on its own (Zhang et al, 1991;Desbois et al, 1991a;Saatcioglu et al, 1993), the oncoprotein overcomes the inactivation of AP-1 activity induced by T3 and RA liganded receptors (Desbois et al, 1991a). This functional interference with the AP-1 pathway probably involves protein-protein interactions between v-erb A and members of the jun/fos family, T3 or RA receptors, or additional proteins crucial for functional AP-1/nuclear receptors interactions.…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of the cell-specific activity of v-erb A in quail myoblasts

et al. 1997

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We have previously shown that v-erb A expression strongly stimulates quail myoblast proliferation and di erentiation without alteration of the triiodothyronine (T3) in¯uence in this cell type. In order to understand the molecular basis of v-erb A action in myoblasts, we have studied the in¯uence of this oncoprotein on c-erb Aa1 encoded T3 nuclear receptor (TRa) activity. In transfection experiments, v-erb A did not inhibit the T3-dependent c-erb Aa1 transcriptional activity in QM7 myoblasts in contrast to its action in HeLa cells. However, it repressed the retinoic acid receptor RARa activity in both cell-types, indicating that v-erb A interactions with T3 or RA mediated transcription signi®cantly di ers. In EMSA experiments using a TRE pa1 probe, T3Ra binds as three complexes in HeLa cells. We have previously identi®ed the slow migrating complex, undetectable in QM7 myoblasts, as a T3R/ RXR heterodimer. Interestingly, v-erb A inhibited binding of this complex in HeLa cells, but did not a ect binding of the two other complexes in QM7 myoblasts. Expression of RXR (g isoform), the TRa dimerization partner absent in proliferating QM7 cells, restored inhibition of c-erb Aa1 transcriptional activity in these cells and abrogated the v-erb A myogenic in¯uence. Lastly, v-erb A induced a T3-independent cerb Aa1 activity in QM7 cells when cotransfected in equimolar ratio with the receptor, by inhibiting AP-1 activity and stimulating transcription of a reporter gene driven by a TRE sequence.

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“…Mutational analysis has de®ned several important regions within the LBD of ERa, required for AF-2 activity. In particular an amphipathic helix near the C-terminus of nuclear receptors is essential for ligand-dependent transcriptional activity (Barettino et al, 1994;Danielian et al, 1992;Durand et al, 1994;Saatcioglu et al, 1993). Crystallographic studies have shown that ligand binding results in the realignment of this helix, enabling interacting proteins to associate (Brzozowski et al, 1997;Shiau et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of human estrogen receptor α at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera

et al. 2002

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Estrogen receptor a (ERa) is a transcription factor that regulates expression of target genes in a ligand-dependent manner. Activation of gene expression is mediated by two transcription activation functions AF-1 and AF-2, which act in a promoter-and cell-speci®c manner. Whilst AF-2 activity is regulated by estrogen (E2) binding, the activity of AF-1 is additionally modulated by phosphorylation at several sites. One of these phosphorylation sites, serine 118 (S118) is of particular interest as its mutation signi®cantly reduces ERa activity. Previous studies have shown that S118 can be phosphorylated by the ERK1/2 mitogen activated protein kinases (MAPK) and by the cyclindependent protein kinase Cdk7. In this study we use antisera that speci®cally recognize ERa phosphorylated at S118 to demonstrate that MAPK phosphorylates S118 in a ligand-independent manner, whereas Cdk7 mediates E2-induced phosphorylation of S118. E2 stimulation of S118 phosphorylation was observed within 10 min of its addition and was maximal at 10 77 M E2. S118 phosphorylation was maximal at 30 min but then declined, such that by 180 min following E2 addition little S118 phosphorylation was evident. S118 phosphorylation was also induced by the partial estrogen antagonist 4-hydroxytamoxifen, but not by the complete antagonist ICI 182, 780. S118 phosphorylation upon addition of the MAPK inducers EGF or PMA followed the expected time courses. Finally, we show that ERa is phosphorylated at S118 in vivo using immunoblotting of extracts prepared from a series of ERa-positive breast tumours.

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A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor).

Cited by 102 publications

References 62 publications

Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator

Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator

Molecular basis of the cell-specific activity of v-erb A in quail myoblasts

Phosphorylation of human estrogen receptor α at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera

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