The c-erb-A protein is a high-affinity receptor for thyroid hormone

Sap, Jan; Múñoz, Alberto; Damm, Klaus; Goldberg, Yves; Ghysdael, Jacques; Leutz, Achim; Beug, Hartmut; Vennström, Björn

doi:10.1038/324635a0

Cited by 1,310 publications

(646 citation statements)

References 47 publications

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“…Human TRs are encoded by two genes, TRα and TRβ (official name THRA and THRB), located on chromosomes 17 and 3, respectively (Sap et al, 1986;Weinberger et al, 1986). TRs are composed of several functional domains: A/B domain, C domain (DNA binding domain, DBD), D domain (hinge domain), and E domain (ligand binding domain, LBD).…”

Section: Molecular Mechanisms Underlying the Transcriptional Regulatimentioning

confidence: 99%

Thyroid hormone action in metabolic regulation

2011

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Thyroid hormone plays pivotal roles in growth, differentiation, development and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms, diverse thyroid hormone response elements, different heterodimeric partners, coregulators, and the cellular location of TRs. In the present review, we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research, thyroid hormone mimetics application, TR isoform-specific knock-in mouse models, and mitochondrion study with highlights in metabolic regulations. Finally, as future perspectives, we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism.

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Section: Molecular Mechanisms Underlying the Transcriptional Regulatimentioning

confidence: 99%

Thyroid hormone action in metabolic regulation

2011

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“…As two point mutations occurred in the DNA binding domain of v-erb A in comparison to c-erb A, the P box amino acid sequence mainly responsible for sequence recognition of speci®c responsive elements is a ected (Sap et al, 1986;Forman and Samuels, 1990). According to the proposal of Fuerstenberg et al (1992), the existence of v-erb A speci®c responsive genes should be postulated.…”

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

confidence: 99%

“…It represents a mutated version of the c-erb Aa protooncogene encoding triiodothyronine (T3) nuclear receptor (Sap et al, 1986;Weinberger et al, 1986) a member of the steroid nuclear receptor together with glucocorticoid, androgen, oestrogen, vitamin D3, or retinoid receptors. The v-erb A oncoprotein di ers from its cellular counterpart by fusion with gag-residues, N-terminal truncation, Cterminal deletion and several point mutations.…”

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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“…Two thyroid hormone receptor genes (a and b) have been identi®ed on the basis of their sequence similarity to the v-erbA gene encoded by the avian erythroblastosis retrovirus and hence originally named c-erbA 1 and 2 (Sap et al, 1986;Weinberger et al, 1986). Unlike their viral homologue, the c-erbA gene products do not exert proliferative e ects but are implicated in the induction of various di erentiation processes such as those of muscle cells (Carnac et al, 1993), oligodendrocytes (Baas et al, 1997) and haematopoietic cells (Gandrillon et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Activation of the thyroid hormone receptor α gene promoter by the orphan nuclear receptor ERRα

et al. 1998

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The superfamily of nuclear receptors comprises transcription factors that depend on a ligand for their activity. In addition, the superfamily includes a number of orphan receptors, for which no ligand is known. We report here that the orphan receptor estrogen receptor related alpha receptor (ERRa) stimulates the expression of the thyroid hormone receptor alpha (TRa) gene promoter. We characterized a responsive site that is both necessary and su cient for ERRa-induced transactivation. In addition, we show that both TRa and ERRa are coexpressed in embryonic intestine, brown fat and heart as well as in the adult gonads. In the testis, expression of both receptors can be found in the seminiferous tubes where it is totally restricted to spermatocytes I. Altogether this suggests that TRa is an in vivo target of ERRa.

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The c-erb-A protein is a high-affinity receptor for thyroid hormone

Cited by 1,310 publications

References 47 publications

Thyroid hormone action in metabolic regulation

Thyroid hormone action in metabolic regulation

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

Activation of the thyroid hormone receptor α gene promoter by the orphan nuclear receptor ERRα

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