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Cheng, Sheue-yann

doi:10.1023/a:1010052101214

Cited by 166 publications

(56 citation statements)

References 51 publications

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“…Thyroid hormone receptors (TRs) 1 belong to a steroid hormone/retinoic acid nuclear receptor superfamily that plays an important role in cell proliferation, differentiation, and homeostasis (1,2). Four different thyroid hormone (T3) binding TR isoforms deriving from alternative splicing of two separate genes are identified.…”

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confidence: 99%

“…Four different thyroid hormone (T3) binding TR isoforms deriving from alternative splicing of two separate genes are identified. They are expressed in tissue-dependent and developmentally regulated fashion (1,2). TR functions not only as a ligand-dependent transcription factor in the presence of ligand but also acts as a constitutive repressor for their target genes in the absence of ligand.…”

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confidence: 99%

“…: 301-496-4280; Fax: 301-480-9676; E-mail: sycheng@helix.nih.gov. 1 The abbreviations used are: TR, thyroid hormone nuclear receptor; TRE, thyroid hormone response element: SRC, steroid hormone receptor co-activator; TSA, trichostatin; HA, hemagglutinin; AD1-HA, cyclin D1 tagged with hemagglutinin; ER, estrogen receptor; FBS, fetal bovine serum; GST, glutathione S-transferase; HDAC, histone deacetylase; Lys-TRE, TRE of the chicken lysozyme gene that is an everted repeat of the half-site binding motifs separated by six nucleotides; mAbC4, monoclonal anti-TR␤1 antibody; RXR␤, retinoic X receptor ␤; F-HDAC, FLAG-tagged HDAC.…”

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Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors

Lin

Zhao

Cheng³

2002

Journal of Biological Chemistry

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Thyroid hormone receptors (TRs) are critical regulators of growth, differentiation, and homeostasis. TRs function by regulating the expression of thyroid hormone (T3) target genes in both ligand-dependent and -independent pathways. Distinct classes of co-regulatory proteins modulate these two pathways. We show here a novel role of cyclin D1 as a T3-independent corepressor for TRs. Cyclin D1 interacted with TR in vitro and in cells in a ligand-independent manner. Cyclin D1 acted to repress both the silencing activity of the unliganded TR and the transcriptional activity of the liganded TR. The repression was not due to the inhibition of the binding of TR to the thyroid hormone response element but by serving as a ligand-independent bridging factor to selectively recruit HDAC3 to form ternary complexes. The repression was augmented by increasing expression of HDAC3 but not by HDAC1 and was alleviated by trichostatin A. Thus, cyclin D1 is a novel ligandindependent co-repressor that opens a new paradigm to understand the molecular basis of the silencing action of TR.

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Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors

Lin

Zhao

Cheng³

2002

Journal of Biological Chemistry

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“…Similar to other NHRs, TRs can be structurally divided into several domains: two conserved activation function domains (AF1 and AF2) and a DNA-binding domain (DBD) connected to the ligand-binding domain (LBD) through a hinge domain (Zhang & Lazar 2000). In humans, there are two TR subtypes, a and b, expressed by two different genes located on chromosomes 17 and 3 respectively (Cheng 2000, Zhang & Lazar 2000. Alternate RNA splicing gives rise to several isoforms for each subtype, some of which cannot respond to thyroid hormone ligands.…”

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confidence: 99%

“…Of the TRa isoforms, only TRa1 exhibits the ability to bind to the native thyroid hormone triiodothyronine (T 3 ), while all the three TRb isoforms have T 3 -binding ability. The expression levels of the various TRs within a given cell depend on both tissue type and developmental stage for a given animal (Cheng 2000).…”

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Analysis of the roles of mutations in thyroid hormone receptor-β by a bacterial biosensor system

Shi¹,

Meng²,

Wood³

2013

Journal of Molecular Endocrinology

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Mutations in thyroid hormone receptors (TRs) often lead to metabolic and developmental disorders, but patients with these mutations are difficult to treat with existing thyromimetic drugs. In this study, we analyzed six clinically observed mutations in the ligand-binding domain of the human TRb using an engineered bacterial hormone biosensor. Six agonist compounds, including triiodothyronine (T 3 ), thyroxine (T 4 ), 3,5,3 0 -triiodothyroacetic acid (Triac), GC-1, KB-141, and CO-23, and the antagonist NH-3 were examined for their ability to bind to each of the TRb mutants. The results indicate that some mutations lead to the loss of ability to bind to native ligands, ranging from several fold to several hundred fold, while other mutations completely abolish the ability to bind to any ligand. Notably, the effect of each ligand on each TRb mutant in this bacterial system is highly dependent on both the mutation and the ligand; some ligands were bound well by a wide variety of mutants, while other ligands lost their affinity for all but the WT receptor. This study demonstrates the ability of our bacterial system to differentiate agonist compounds from antagonist compounds and shows that one of the TRb mutations leads to an unexpected increase in antagonist ability relative to other mutations. These results indicate that this bacterial sensor can be used to rapidly determine ligand-binding ability and character for clinically relevant TRb mutants. Key Words" thyroid hormone receptor " ligand-binding assay " hormone receptor mutations " engineered biosensor

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TSH adenoma and syndrome of resistance to thyroid hormones—Two cases report of syndrome of inappropriate secretion of thyrotropin

et al. 2021

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SITSH (syndrome of inappropriate secretion of thyrotropin) is a rare clinical state defined as uninhibited serum thyroid stimulating hormone in the presence of elevated thyroid hormone. This state is complicated and mainly caused by the abnormal feedback of hypothalamus–pituitary thyroid axis. The TSH adenoma (TSH‐oma) and resistance to thyroid hormones (RTH) are the main etiologies of SITSH. As is well known that the treatment strategies of RTH and TSH‐oma are apparently different, thus identifying the difference between RTH and TSH‐oma is of great significance for the diagnosis and treatment of SITSH. Case description A 62‐year‐old man with a state of elevated thyroid hormones and inappropriate elevated serum TSH level was hospitalized in 2016. Results of the pituitary enhanced magnetic resonance imaging and the somatostatin test respectively demonstrated a space‐occupying lesion of pituitary and an elevated serum sex hormone binding globulin (SHBG) and inhibited TSH secretion, which indicated the occurrence of TSH‐oma. In 2019, a 23‐year‐old girl with a state of elevated thyroid hormones and inappropriate normal serum TSH was hospitalized. Interestingly, whole exome sequencing detection suggested a pathogenic mutation in thyroid hormone receptor β (THRB) gene, which has been shown to be associated with RTH. Conclusions The difference between TSH‐oma and RTH ought to be clarified for their accurate diagnose and treatment. The clinical experiences of the two cases reported here suggest that more detail information such as family medical history, serum SHBG level, and THRB gene test is helpful for the diagnose and treatment of TSH‐oma and RTH. Additionally, we also summarized the identification points, diagnosis process, and treatment strategies for these two rare diseases.

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Cited by 166 publications

References 51 publications

Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors

Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors

Analysis of the roles of mutations in thyroid hormone receptor-β by a bacterial biosensor system

TSH adenoma and syndrome of resistance to thyroid hormones—Two cases report of syndrome of inappropriate secretion of thyrotropin

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