Disease relevance of ESRRB

• In contrast, hERRbeta was only observed in 9.1% of ovarian cancers [1].
• By RT-PCR experiments, we found that ERR-1, but not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell lines as well as in primary osteoblastic cell populations derived from normal human bone [2].
• We now report that the HTLV-I LTR contains two distinct Ets1-responsive regions, ERR-1 and ERR-2 [3].

High impact information on ESRRB

• Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling [4].
• We have found that the SHP promoter is also activated by the estrogen receptor-related receptor gamma (ERRgamma) but not the related ERRalpha and ERRbeta isoforms [5].
• To better understand the mechanism by which DNA specificity is achieved, the solution structure of the DNA-binding domain of hERR2 (residues 96-194) consisting of the two putative zinc fingers and the requisite 26-amino acid CTE was analyzed by multidimensional heteronuclear magnetic resonance spectroscopy [6].
• Unlike steroid and retinoid receptors, which associate with DNA as dimers, human estrogen related receptor-2 (hERR2) belongs to a growing subclass of nuclear hormone receptors that bind DNA with high affinity as monomers [6].
• Transient transfection of different cell lines with a steroid-responsive reporter plasmid and receptor expression plasmids revealed that transcriptional activity mediated by GR in response to agonists was strongly suppressed by coexpression of ERR2 [7].

Biological context of ESRRB

• Using fluorescence in situ hybridization, we have mapped the human ESRRA gene to chromosome 11q12-q13 and the human ESRRB gene to chromosome 14q24 [8].
• ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE) [4].
• The inhibitory activity of ERR2 is cell-specific and also receptor-specific because transactivation mediated by the progesterone receptor is unaffected by ERR2 [7].
• The three human ERRbeta-splicing isoforms have different transcriptional activities when measured on an estrogen response element-driven luciferase reporter in transfection assays [9].
• Embryo lethality of ERRbeta-null mice indicated that ERRbeta is essential for embryo development [9].

Anatomical context of ESRRB

• RT-PCR showed that ERRalpha and ERRgamma transcripts were detected in most cell lines and xenografts, whereas ERRbeta was detected in normal epithelial cells and few immortalized cell lines but not in most cancer lines [10].
• RT-PCR was performed to analyze the expression of hERRalpha, hERRbeta, hERRbeta-2, and hERRgamma mRNA in five ovarian cancer cell lines as well as 33 samples of ovarian cancer and 12 samples of normal ovary [1].
• RT-PCR analysis showed that short-form hERRbeta has a wide distribution in the 24 of 27 human tissues and cell lines tested, whereas hERRbeta2 and hERRbeta2-Delta10 were only expressed in testis and kidney [9].

Associations of ESRRB with chemical compounds

• Together, these results suggest that hERR1 and hERR2 activate gene transcription through a mechanism different from most of the previously characterized steroid hormone receptors [11].

Physical interactions of ESRRB

• By gel mobility shift assay, the interaction of Ets1 with the downstream ERR-1-binding region was found to be more stable than its interaction with the upstream ERR-2 region [3].

Other interactions of ESRRB

• This study was conducted to determine whether human ERRalpha, ERRbeta, and ERRgamma might be involved in the tumorigenesis of ovarian cancer [1].
• Our observations provide evidence that the nuclear orphan receptor ERR2 acts as an endogenous modulator of GR transcriptional activity [7].

Analytical, diagnostic and therapeutic context of ESRRB

• Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR [12].
• Sequence analysis revealed that hERRbeta2 and hERRgamma2 respectively share 95% and 77% overall aa sequence identity with hERR2 [12].

References