Role Of Coactivators And Cosuppressors In The Mediation Of Estrogen Action

As described in an earlier section, estrogen induces its physiological action by binding with specific receptors in the plasma membrane and eventually triggering multiple gene activations to carry out cell proliferation and differentiation. It is now established that estrogen receptors themselves cannot carry out the transcription alone, but need an interaction with a complex of coregulatory proteins called coactivators or corepressors that act as signaling intermediates between ER and gene transcription machinery.133 The replacement of cosuppressor and simultaneous binding of coactivator and ligand to the hormone-dependent activation domain (AF-2) of ER is essential in this transcription machinery.

On the basis of their ability to interact with ER, several coactivators are known. Of these proteins, the most notable are ERAP160, RIP140, and SRC1. RIP 140 interacts with the ligand binding domain (LBD) of ERa. SRC1 (also called p160/NcoA-1/ERAP-160), SRC2 (TIF2/GRIP-1), and SRC-3 (AIBI/RAC-3/TRAM-1) are not only transcription mediators for ligand-dependent AF2 of ER, but they are also involved in ligand-independent interaction with activating factor-1 (AF-1) of ERa and with ERp through phosphorylation of its AF-1 via MAPK. The SRC-1 complex also contains SRA, which mediates transactivation via AF-1. ERoc/ERp can also activate gene transcription via SRC 1 (128). Another protein remaining in combination with SRC1 is p300/CBP. SRC1 and p300/CBP contain intrinsic acetyl transferase activity and can interact with other histone acetyl tranferases. Acetylation of histone brings about the activation of the transcription of specific genes by AF-1 and AF-2 of ER. The specific peptides of SRC1 are known to interact with ERa and ERp.144 Another coactivator is the estrogen-receptor-related receptors (ERRs). These are of three types, a, p, and y. They identify with both ERs and exhibit similar, but distinct, biochemical and transcriptional activities as ERa and ERp. However, ERRs do not bind natural estrogen but, rather, interact with transcriptional coactivators inside the cell in the absence of ligands.145

Aloe and Your Health

Aloe and Your Health

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