Transcriptional coregulator RIP140: an essential regulator of physiology

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   Figure 1

   RIP140 a switch coregulator. Cartoon of RIP140 protein showing different known domains (RD1–4) and interaction motifs (LXXLL and LXXML) (Christian et al. 2006) with transcription factors and enzymes, which modify histones, ie, histone deacetylase (HDAC) and CREB-binding protein (CBP). RIP140 can function both as a coactivator (ON switch) as well as a corepressor (OFF switch). Key processes regulated by RIP140 are highlighted in green (activation) and red (repression) boxes, respectively.
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   Figure 2

   Biological processes regulated by RIP140. Ovary: Pre-ovulatory follicles with granulosa cells (pink) lining the follicle. The cumulus oocyte complex, which is the oocyte surrounded by cumulus granulosa cells (darker blue) is shown in an unexpanded state on left. After the LH surge, RIP140 activates amphiregulin (Areg) expression, which further activates downstream enzymes that synthesise the cumulus matrix. This results in cumulus expansion, i.e., cumulus granulosa cells spread on a self-synthesised matrix (lighter blue cells), shown on right (Nautiyal et al. 2010, Ochsner et al. 2003a,b). Mammary gland: Shown on the left is a mammary fat pad with rudimentary epithelium at the base representing a pre-pubertal mouse mammary gland. RIP140 activates mitogens and factors that are essential for mammary gland development, side branching and differentiation (Right). These factors include Areg, PGR, STAT5a and Ccnd1, which are all ER target genes that are coactivated by RIP140 in the mammary gland (Nautiyal et al. 2013a,b). Adipose tissue: (Extreme left) Fat storing WAT that is composed of adipocytes and M2 macrophages. WAT adipocytes expand in size on exposure to high-fat diet to meet the increasing demands of fat storage and also have an increased infiltration of macrophages, which are of the M1 (i.e., inflammatory type). Loss of RIP140 promotes the formation of BAT. RIP140 KO animals are lean and show a BAT adipose phenotype. BAT (extreme right) has smaller fat droplets and is abundant in mitochondria and generates heat. Loss of RIP140 from macrophages promotes the formation of Beige fat depots, which are adipocytes within the WAT that are intermediary between WAT and BAT. This is called ‘browning of fat,’ which is promoted by loss of RIP140 (Liu et al. 2015b).

• © 2017 Society for Endocrinology