Antibodies to Estrogen-Related Receptors
(ERR alpha, -beta, and -gamma)

Introduction

Estrogen-related receptors (ERRs) are orphan members of the nuclear receptor super family of ligand-dependent transcription factors. Unlike estrogen receptors (ERs), ERRs are unresponsive to natural estrogens and activate transcription constitutively, interacting with required coactivators and DNA- binding elements in the absence of ligand. All the ERR family members - ERR alpha, beta, and gamma (ERR 1, 2, and 3) - share an almost identical DNA-binding domain, which has 68% amino acid identity with that of estrogen receptor.

The orphan nuclear receptor estrogen related receptor alpha (ERR alpha, NR3B1) is a constitutively active transcription factor that controls multiple processes, most notably mitochondrial function. ERR alpha preferentially binds to a nine nucleotide extended half-site sequence TNAAGGTCA, referred to as the ERRE, as either a monomer or a dimer, although how the mode of DNA binding is dictated remains to be determined.

ERR beta plays a critical functional role in placental development.ERR beta also can act as a repressor of transcriptional activity mediated by the glucocorticoid receptor (GR). ERR beta binds as a monomer to the extended half-site TNAAGTGCA and as a homodimer to the estrogen response element (ERE), palindromic thyroid hormone response element (TRE(pal)), and SF-1 response element, but not to the glucocorticoid response element (GRE).

ERR beta mutations lead to abnormal development of the chorion and defective diploid trophoblast proliferation, and are lethal during midgestation. Estrogen receptor-related receptor (ERR gamma), a NR3 Steroid Receptor, has been suggested to affect differentia¬tion of the brain, heart, and kidney. ERR gamma binds as a monomer to an extended half-site of the ERRE type (TCAAGGTCA). ERR gamma has been shown to interact with PGC-1 alpha and has been implicated in the regulation of mitochondrial energy metabolism.

In humans, ERR gamma pre-mRNA undergoes extensive alternative splicing at the 5’ end, yielding at least six mRNA splice variants and two protein isoforms that differ by 23 amino acids in the N terminus. ERR gamma has been shown to be over¬expressed in breast tumors, and its expression is correlated with levels of ErbB4, a likely indicator of preferred clinical course. As a result, ERR gamma has been suggested to be a potential biomarker for favorable clinical course and, possibly, hormonal sensitivity, and as a candidate target for therapeutic development.

Antibody Panel to ERRs

Acris Antibodies offers a range of polyclonal antibodies for the detection of ERRs by Immunohistochemistry (on Paraffin embedded tissues) or Western blotting.

Fig.1: Immunohistochemical staining of ERR alpha in human breast tissue using antibody SP4129P

Fig.2: Immunohistochemical staining of ERR alpha in human breast tissue using antibody SP4130P

Fig.3: Immunohistochemical staining of ERR beta in human testis using antibody SP4131P

Fig.4: Immunohistochemical staining of ERR gamma in breast cancer using antibody SP4133P

Antibody Panel to ERRs

ERRs, Estrogen Related Receptors –antibody.

Literature

Estrogen-related receptor alpha1 transcriptional activities are regulated in part via the ErbB2/HER2 signaling pathway. Ariazi EA, Kraus RJ, Farrell ML, Jordan VC, Mertz JE. Mol Cancer Res. 2007 Jan;5(1):71-85.

A single nucleotide in an Estrogen Related Receptor alpha site can dictate mode of binding and PGC-1 alpha activation of target promoters. Barry JB, Laganiere J, Giguere V. Mol Endocrinol. 2006 Feb;20(2):302-10.

Cavallini A, Notarnicola M, Giannini R, Montemurro S, Lorusso D, Visconti A, Minervini F, Caruso MG. Oestrogen receptor-related receptor alpha (ERR alpha) and oestrogen receptors (ER alpha and ER beta) exhibit different gene expression in human colorectal tumor progression. Eur J Cancer. 2005 Jul; 41(10): 1487-94.

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