A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor.

Baniahmad, Aria; Köhne, Anja Carola; Renkawitz, Rainer

doi:10.1002/j.1460-2075.1992.tb05140.x

Cited by 276 publications

(201 citation statements)

References 43 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…This observation, however, does not preclude interaction of a corepressor protein with a different domain within the carboxy terminus of ARP-1/COUP-TFII, as has been demonstrated for Rev-erbA␣ or RVR (13). Second, deletion of the AF-2 AD core of TR␤ results in a strong constitutive silencer, which is unable to release a corepressor protein and to activate transcription upon binding of a ligand (3,4,66), while the presence of the AF-2 AD core is critical for repressor activity of ARP-1/COUP-TFII. The finding that a domain which is involved in transactivation by other receptors is required for repressor activity of ARP-1/COUP-TFII is puzzling.…”

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

Functional Domains of the Human Orphan Receptor ARP-1/ COUP-TFII Involved in Active Repression and Transrepression

Achatz¹,

Hölzl²,

Speckmayer³

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

The orphan receptor ARP-1/COUP-TFII, a member of the chicken ovalbumin upstream promoter transcription factor (COUP-TF) subfamily of nuclear receptors, strongly represses transcriptional activity of numerous genes, including several apolipoprotein-encoding genes. Recently it has been demonstrated that the mechanism by which COUP-TFs reduce transcriptional activity involves active repression and transrepression. To map the domains of ARP-1/COUP-TFII required for repressor activity, a detailed deletion analysis of the protein was performed. Chimeric proteins in which various segments of the ARP-1/COUP-TFII carboxy terminus were fused to the GAL4 DNA binding domain were used to characterize its active repression domain. The smallest segment confering active repressor activity to a heterologous DNA binding domain was found to comprise residues 210 to 414. This domain encompasses the region of ARP-1/COUP-TFII corresponding to helices 3 to 12 in the recently published crystal structure of other members of the nuclear receptor superfamily. It includes the AF-2 AD core domain formed by helix 12 but not the hinge region, which is essential for interaction with a corepressor in the case of the thyroid hormone and retinoic acid receptor. Attachment of the nuclear localization signal from the simian virus 40 large T antigen (Flu tag) to the amino terminus of ARP-1/COUP-TFII abolished its ability to bind to DNA without affecting its repressor activity. By using a series of Flu-tagged mutants, the domains required for transrepressor activity of the protein were mapped.

show abstract

Section: Discussionmentioning

confidence: 88%

“…Transcriptional repression by the unliganded TR␤ has been studied extensively (2)(3)(4)16). The segment comprising residues 175 to 442 of the TR␤ LBD has been defined as the active silencing domain (3,4) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Functional Domains of the Human Orphan Receptor ARP-1/ COUP-TFII Involved in Active Repression and Transrepression

Achatz¹,

Hölzl²,

Speckmayer³

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Several nuclear receptors (TR , v-erbA, RAR ) are reported to exert silencing activity through their C-terminal domain (Baniahmad et al 1992;Casanova et al 1994;. Possibly supporting this notion, Baniahmad et al (1995) recently mapped the silencing activity of TR to a region that includes a sequence corresponding to the C-terminal end of RXR 1 C2 and RXR 448.…”

Section: Discussionmentioning

confidence: 92%

**Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR**

et al. 1996

View full text Add to dashboard Cite

show abstract

“…Di erent hypotheses have been proposed to account for the v-erb A antagonism. It could compete with the receptors for binding to response elements, resulting in transcriptional silencing from these elements (Sap et al, 1989;Damm et al, 1989;Sharif and Privalsky, 1991;Baniahmad et al, 1992). Alternatively, it could trap the receptors themselves or their heterodimerization partners into non functional complexes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1997

View full text Add to dashboard Cite

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.

show abstract

A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor.

Cited by 276 publications

References 43 publications

Functional Domains of the Human Orphan Receptor ARP-1/ COUP-TFII Involved in Active Repression and Transrepression

Functional Domains of the Human Orphan Receptor ARP-1/ COUP-TFII Involved in Active Repression and Transrepression

**Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR**

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

Contact Info

Product

Resources

About