c-erbA Protooncogenes Mediate Thyroid Hormone-Dependent and Independent Regulation of the Rat Growth Hormone and Prolactin Genes

Forman, Barry M.; Yang, Chen; Stanley, Frederick; Casanova, Juan; Samuels, Herbert H.

doi:10.1210/mend-2-10-902

Cited by 129 publications

(56 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As RXR/T3R heterodimers could induce a potent transcriptional activation of reporter gene expression on some synthetic TREs independently of T3 presence (Force et al, 1994), we postulated a similar activity of a v-erb A/c-erb A heterodimer in QM7 cells. Conformational change induced by this physical interaction could account for the activation of such heterodimers, as previously reported for chick cerb A/rat c-erb A heterodimer (Forman et al, 1988). Unfortunately, we have been unable so far to detect verb A/T3R complexes using a TRE pa1 or a DR4 motif.…”

Section: V-erb a Induces A T3 Independent C-erb A Activity In Avian Msupporting

confidence: 50%

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

Section: V-erb a Induces A T3 Independent C-erb A Activity In Avian Msupporting

confidence: 50%

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

et al. 1997

View full text Add to dashboard Cite

show abstract

“…We chose GH4C1 cells to construct a yeast two-hybrid cDNA library for several reasons. First, these cells contain virtually all nuclear hormone receptors at levels (ϳ10,000 per cell) similar to that found in somatotrophs and other hormone responsive tissues in vivo (15,45,49). Second, regulation of the endogenous growth hormone gene by thyroid hormone (T3) and glucocorticoids, and of the prolactin gene by estrogens, FIG.…”

Section: Resultsmentioning

confidence: 59%

A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein

Mahajan

Samuels

2000

Molecular and Cellular Biology

Self Cite

190

View full text Add to dashboard Cite

We describe the cloning and characterization of a new family of nuclear receptor coregulators (NRCs) which modulate the function of nuclear hormone receptors in a ligand-dependent manner. NRCs are expressed as alternatively spliced isoforms which may exhibit different intrinsic activities and receptor specificities. The NRCs are organized into several modular structures and contain a single functional LXXLL motif which associates with members of the steroid hormone and thyroid hormone/retinoid receptor subfamilies with high affinity. Human NRC (hNRC) harbors a potent N-terminal activation domain (AD1), which is as active as the herpesvirus VP16 activation domain, and a second activation domain (AD2) which overlaps with the receptorinteracting LXXLL region. The C-terminal region of hNRC appears to function as an inhibitory domain which influences the overall transcriptional activity of the protein. Our results suggest that NRC binds to liganded receptors as a dimer and this association leads to a structural change in NRC resulting in activation. hNRC binds CREB-binding protein (CBP) with high affinity in vivo, suggesting that hNRC may be an important functional component of a CBP complex involved in mediating the transcriptional effects of nuclear hormone receptors.Nuclear hormone receptors comprise a superfamily of ligand-dependent transcription factors involved in controlling diverse cellular processes, including growth, differentiation, development, and homeostasis (37). The nuclear hormone receptor superfamily includes type I receptors which mediate the effects of glucocorticoids (glucocorticoid receptor , and the PPARs. These receptors share a similar modular structure consisting of an Nterminal A/B domain, a DNA-binding C domain, and a D, E, and F ligand-binding domain (LBD) (4, 37). The DNA-binding C domain is highly conserved among members of type I and type II nuclear hormone receptors. Although the LBDs of nuclear hormone receptors (ϳ300 amino acids) are diverse in sequence, accounting for ligand specificity, they exhibit certain similarities in their overall structure (4, 13). Thus, the LBDs of all nuclear receptors are organized into 12 helical regions which play an important role in determining the conformation of the LBD in the presence and absence of ligand (59) and in mediating heterodimerization of type II receptors with the RXRs (2, 13).[Ligand-dependent conformational changes in the LBD are thought to recruit coactivators or coregulators to the DNAbound receptor, which leads to transcriptional activation (37). The activation function mediated through the LBD has been referred to as activation function 2 (AF2) (38, 54). The majority of the coactivators, identified in a yeast two-hybrid screen, fall into two main groups: the p160/SRC family (SRC-1 (5,20,28). Coactivators which fall outside these groups include PGC-1 (44), ARA70 (62), p/CAF (3, 60), and NRIF3, which exhibits specificity for only the TRs and the RXRs (33). Using a biochemical approach, another class of factors have been identified...

show abstract

“…Rat TRa-1 is also able to activate transcription in a T 3 -independent fashion in pituitary GH4C1 cells but not in several other cell lines (63,64). In addition, the regulatory regions of the Rous sarcoma virus and human immunodeficiency virus type 1 are activated in transfected cells by TRa-1, but not TRb-1, independently of T 3 (65,66).…”

Section: Hormone-independent Activities Of Trmentioning

confidence: 87%