Abstract
Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.
Highlights
Estrogen Signaling in Breast Cancer CellsEstrogens are steroid hormones that regulate growth and differentiation of a large number of target tissues such as the mammary gland, the reproductive tract and skeletal and cardiovascular systems [1]
Almost 20 years ago, one of the main goals in the field of nuclear receptor (NR) biology was to identify interacting partners acting as transcriptional coregulators
The present review focuses on the transcriptional coregulator RIP140/Nuclear receptor-interacting protein 1 (NRIP1) which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways
Summary
Estrogens are steroid hormones that regulate growth and differentiation of a large number of target tissues such as the mammary gland, the reproductive tract and skeletal and cardiovascular systems [1]. Most of these events are mediated through two distinct intracellular receptors, ERα and ERβ, which belong to the superfamily of nuclear receptors. Ligand binding induces a conformational change that facilitates the recruitment of a large set of coactivator proteins [2] These transcription mediators act either by stabilizing the formation of a transcription preinitiation complex or by facilitating chromatin disruption through various enzymatic activities that target histone tails. The estrogen signaling pathway is finely regulated by multiple post-translational modifications which regulate its function and play important roles in physiopathology [5]
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