The nuclear receptor transcriptional activity is regulated by coregulators including coactivators (SRC-1, SRC-2 and SRC-3, RIP140 etc.) and co-repressors (HDAC1, HDAC2 and HDAC3, SMRT and NoCRs). The transactivational potency of agonist bound progesterone receptor (PR) can be significantly enhanced by increasing the cellular level of members of the steroid receptor coactivator (SRC/p160) family of coregulators. The coactivators of NF-kB include P300/CBP, p/CAF, and p160 proteins (SRC-1, SRC-2 and SRC-3). CBP/p300 and the p160 (HDACs) proteins both possess intrinsic histone acetylase (HAT) activity, which is necessary to open the chromatin structure through an acetylation-induced conformation change in histone protein. The coactivators of nuclear receptors provide an bridging apparatus between nuclear receptor and the transcription machinery. It has recently been shown that Orphan receptor SF-1, which regulates the cAMP stimulated expression of human steroidenic acute regulatory protein gene DAX-1, interacts with RIP140. The steroid receptor co activator 2 (SRC-2) knockout mice exhibited severe reproductive defects in both sexes, the males are hypofertile with developmental defect in spermatogenesis and age-dependent testicular degeneration. The females revealed a significant hypo-fertility phenotype die to partial placental hypoplacia (1). The components of the nuclear receptor NF-kB include SMRT, NCoR, HDAC1, HDAC2 and HDAC3, the SMRT and NCoR do not have an intrinsic enzyme activity , but they can trigger the catalytic activity of histone deacetylase (HDAC) for deacetylation of histone proteins (2). HDAC1–3 belongs to the class I histone deacetylases that includes HDAC1, 2, 3, 8, and 11 (3). The class II histone deacetylases include HDAC4, 5, 6, 7, 9, and 10. The catalytic activity of HDACs is required for deacetylation of histones and transcription factors in the regulation of transcription.
NuCR-2 is also known as GRIP-1 is involved in skeletal myogenic differentitation by interacting with basic helix-loop-helis (bHLH) and myogenic regulatory factors (MRFs) including MyoD, myogenin, Myf5 and MRF4 (4), and with class II receptor (TRa, VDR, RARa, RXRa) which show high degree of sequence homology with SRC-11 (4). NuCR2 is expressed in 2 isoforms a and b with MW in 160 kDa range and is distributed in both cytoplasm and nucleus, the distribution is regulated y cell differentiation. NuCR2 as two activation domains (AD1 and AD2)positioned in the C-terminal regionand are responsible for recruiting secondary regulators. The AD1 domain interacts with HDAC and related CRE-binding proteins, where as AD2 recruits Arginine methyl transferases such as co-activator-associated Arginine Transferase 1 (CARM1) (5).
FabGennix International Inc. has produced an epitope-specific antibody to NuCR2 protein. The C-terminal epitope covers the HDAC binding domain (aa 1029-1045 of the short isoform a and 1457-1462 of the large b isoform). The polyclonal antibodies to NuRC2 label a 160 kDa protein in PC-NuCR2 sample
The NuCR2-specific antiserum has no cross reactivity against any other protein tested so far. FabGennix Inc. also provides Western blot positive controls for NuCR2 (PC-NuCR2) protein in ready-to-use buffer for SDS-PAGE and western blotting applications. FabGennix Int. Inc., will conjugate NuRC2 antibodies to fluorphores (FITC, Cy5, Rhodamine etc.) and or biotin/enzymes (ALK/HRP). Please inquire about pricing and availability. Limited quantities of antigenic blocking peptide and western blot positive controls are also available.
For research use only, not for diagnostic or therapeutic use.
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