ROR-γ: The Third Member of ROR/RZR Orphan Receptor Subfamily That Is Highly Expressed in Skeletal Muscle

Hirose, Takahisa; Smith, Robert J.; Jetten, Anton M.

doi:10.1006/bbrc.1994.2902

Cited by 204 publications

(193 citation statements)

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“…This contrasts with the more selective expression of RORB and RORC, two other members of the same family (Jetten, 2004). It was reported that RORB is expressed specifically in the brain (Carlberg et al, 1994), and RORC is found at high levels in the skeletal muscle (Hirose et al, 1994). However, we do not have any evidence to rule out the possibility that RORB and RORC also play some role in tumorigenesis in vivo.…”

Section: Discussioncontrasting

confidence: 81%

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RORA, a large common fragile site gene, is involved in cellular stress response

et al. 2006

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Common fragile sites (CFSs) are large genomic regions present in all individuals that are highly unstable and prone to breakage and rearrangement, especially in cancer cells with genomic instability. Eight of the 90 known CFSs have been precisely defined and five of these span genes that extend from 700 kb to over 1.5 Mb of genomic sequence. Although these genes reside within some of the most unstable chromosomal regions in the human genome, they are highly conserved evolutionarily. These genes are targets for large chromosomal deletions and rearrangements in cancer and are frequently inactivated in multiple tumor types. There is also an association between these genes and cellular responses to stress. Based upon the association between large genes and CFSs, we began to systematically test other large genes derived from chromosomal regions that were known to contain a CFS. In this study, we demonstrate that the 730 kb retinoic acid receptor-related orphan receptor alpha (RORA) gene is derived from the middle of the FRA15A (15q22.2) CFS. Although this gene is expressed in normal breast, prostate and ovarian epithelium, it is frequently inactivated in cancers that arise from these organs. RORA was previously shown to be involved in the cellular response to hypoxia and here we demonstrate changes in the amount of RORA message produced in cells exposed to a variety of different cellular stresses. Our results demonstrate that RORA is another very large CFS gene that is inactivated in multiple tumors. In addition, RORA appears to play a critical role in responses to cellular stress, lending further support to the idea that the large CFS genes function as part of a highly conserved stress response network that is uniquely susceptible to genomic instability in cancer cells.

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Section: Discussioncontrasting

confidence: 81%

“…It consists of three members: RORA (also named NRF1 by the Nuclear Receptor Nomenclature Committee), RORB (NRF2) (Carlberg et al, 1994) and RORC (NRF3, or TOR) (Hirose et al, 1994). It has been demonstrated that these receptors are critical in the regulation of a number of physiological processes.…”

Section: Introductionmentioning

confidence: 99%

RORA, a large common fragile site gene, is involved in cellular stress response

et al. 2006

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“…The ROR/RZR subfamily of orphan nuclear receptors is a recent addition to the nuclear receptor family and comprises the following members: ROR 1, ROR 2, ROR 3, ROR /RZR and ROR , Giguère et al 1994, Hirose et al 1994. The members of this subfamily bind as monomers preferentially to an AGGTCA core motif preceded by an A/T-rich region (Giguère et al 1994).…”

Section: Introductionmentioning

confidence: 99%

“…ROR /RZR is abundantly expressed in the hypothalamus, the pineal gland and the thalamus . ROR is highly expressed in skeletal muscle and may play a role in muscle development (Hirose et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Activation of the mouse oxytocin promoter by the orphan receptor RORalpha

Chu

Zingg

1999

Journal of Molecular Endocrinology

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Although an increasing number of nuclear orphan receptors have recently been identified, the number of known naturally occurring genes that are directly regulated by orphan receptors is still small. We have shown previously that the gene encoding the neuropeptide oxytocin (OT) is negatively regulated by the orphan receptors chicken ovalbumin upstream transcription factor I (COUP-TFI) and II. Here we show that the mouse OT gene promoter is activated by ROR , a representative of the ROR/RZR orphan receptor subfamily. Using promoter/chloramphenicol acetyltransferase reporter constructs in heterologous transfection assays, we determined that ROR action induces a <6-fold increase in promoter activity. By 5 and 3 deletion analysis, DNase footprint analysis and electrophoretic mobility shift assays, we found that ROR action is mediated by two 14 bp regions centered at 160 and 180 nucleotides upstream of the transcriptional initiation site. Both sites contain significant sequence identities with an established ROR recognition sequence. Mutations in either or both of these sites reduce significantly RORinduced activation of the OT promoter. In view of the strong transcriptional activation exerted by ROR on the OT gene promoter and the widespread distribution of different members of the ROR/RZR family, interactions between ROR/RZR isoforms and the OT gene may form part of the multifactorial regulatory mechanisms that control OT gene expression in different tissues.

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“…RORβ knockout mice display a ducklike gait, transient male infertility, abnormal circadian behavior and retinal degeneration [52]. RORγ is found at high levels in skelekal muscle and thymocytes [53,54]. Analysis of RORγ knockout mice revealed significant roles of RORγ in both thymocyte development and lymphoid organogenesis [55].…”

Section: Rors Drug Targets For Cns and Cholesterol-related Diseasesmentioning

confidence: 99%

Orphan nuclear receptors in drug discovery

Shi

2007

Drug Discovery Today

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SummaryOrphan nuclear receptors provide a unique resource for uncovering novel regulatory systems that impact human health and provide excellent drug targets for a variety of human diseases. Ligands of nuclear receptors have been used in a number of important therapeutic areas, such as breast cancers, skin disorders, and diabetes. Orphan nuclear receptors, therefore, represent a tremendous opportunity in understanding and treating human diseases. This review highlights advances and potentials of using orphan nuclear receptors, in particular PPARs, Nurr1, RORs, and TLX as targets for drug discovery in diabetes and obesity, neurodegenerative diseases, and other related disorders.

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ROR-γ: The Third Member of ROR/RZR Orphan Receptor Subfamily That Is Highly Expressed in Skeletal Muscle

Cited by 204 publications

References 0 publications

RORA, a large common fragile site gene, is involved in cellular stress response

RORA, a large common fragile site gene, is involved in cellular stress response

Activation of the mouse oxytocin promoter by the orphan receptor RORalpha

Orphan nuclear receptors in drug discovery

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