Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors [].
This entry includes Fcf2 from budding yeasts and DNTTIP2 from animals. Fcf2 is involved in pre-rRNA processing []. DNTTIP2 regulates the transcriptional activity of DNTT and ESR1 [, ].
GREB1 (gene regulated in breast cancer 1 protein) is a ESR1 (estrogen receptor 1)-upregulated protein that may regulate estrogen action and it is associated with estrogen-stimulated cell proliferation []. It acts as a regulator of hormone-dependent cancer growth in breast, ovarian and prostate cancers [, , , ]. This protein may be a target to inhibit tumour-promoting pathways both downstream and independent of ESR1 as a possible treatment strategy.This entry represents a protein family that includes Protein GREB1 and similar proteins from chordates.
GREB1 (gene regulated in breast cancer 1 protein) is a ESR1 (estrogen receptor 1)-upregulated protein that may regulate estrogen action and it is associated with estrogen-stimulated cell proliferation []. It acts as a regulator of hormone-dependent cancer growth in breast, ovarian and prostate cancers [, , , ]. This protein may be a target to inhibit tumour-promoting pathways both downstream and independent of ESR1 as a possible treatment strategy.This entry represents the C-terminal domain of GREB1 and similar proteins, which may adopt a twisted α/β structure comprising parallel β-sheetσ connected by α-helices that surround the sheet, as revealed from structure predictions.
GREB1 (gene regulated in breast cancer 1 protein) is a ESR1 (estrogen receptor 1)-upregulated protein that may regulate estrogen action and it is associated with estrogen-stimulated cell proliferation []. It acts as a regulator of hormone-dependent cancer growth in breast, ovarian and prostate cancers [, , , ]. This protein may be a target to inhibit tumour-promoting pathways both downstream and independent of ESR1 as a possible treatment strategy.This entry represents a the N-terminal domain of GREB1 and similar proteins, whose function is not yet known. Structure predictions suggest that it may have an α/β fold.
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the fourth (C-terminal) repression domain of nuclear receptor-interacting protein 1 [, ].
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the third repression domain of nuclear receptor-interacting protein 1 [, ].
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the second repression domain of nuclear receptor-interacting protein 1 [, ].
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the first (N-terminal) repression domain of nuclear receptor-interacting protein 1 [, ].
Histone-lysine N-methyltransferase 2D (KMT2D, also known as MLL2; ) is a catalytic component of the MLL2/3 complex (also named ASCOM complex) []and methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. KMT2D is recruited by ESR1 and acts as a coactivator of the oestrogen receptor alpha [].
Activating signal cointegrator 1 (TRIP4) is a transcription coactivator that interacts with nuclear receptors, including thyroid hormone receptor [], the androgen receptor []and ESR1 [], provided ligand is bound to the receptor. This interaction facilitates nuclear receptor-mediated transcription. TRIP4 contains a C4-type zinc finger. It is polyufmylated by the UFM1-conjugating system and deufmylated by the protease UFSP2; ufmylation promotes the recruitment of additional transcriptional coactivators []. This entry also includes the uncharacterized proteins C1A6.01c from the fission yeast and Rqt4 from baker's yeast. Rqt4 is part of the RQC trigger (RQT) complex that activates the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation [].
The AFF (AF4/FMR2) family includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the cell nucleus and are involved in regulation of gene expression [, ].In humans, AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs) [, ].This entry also includes Drosophila AF4 protein homologue Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila [].This entry represents the C-terminal domain homology domain (CHD) that is conserved among AF4/FMR2 family proteins, including AFF1, AFF2, AFF3, and AFF4. This domain consists of eight helices and is distantly related to tetratricopeptide repeat motifs. The CHD domain mediates the formation of an AFF4 homodimer or an AFF1-AFF4 heterodimer. []. This domain is essential for AFF4 interaction with Transcription Start Site (TSS)-associated histone H3K27 whose acetylation signals SEC to regulate transcriptional elongation of the ESR1 gene []. Depletion of AFF4 reduces expression of ESR1, and, consequently inhibits breast cancer cell growth [].
Activator protein-2 (AP-2) transcription factors constitute a family of closely related and evolutionarily conserved proteins that bind to the DNA consensus sequence 5'-GCCNNNGGC-3' and stimulate target gene transcription [, ]. Five different isoforms of AP-2 have been identified in mammals, termed AP-2 alpha, beta, gamma, delta and epsilon. Each family member shares a common structure, possessing a proline/glutamine-rich domain in the N-terminal region, which is responsible for transcriptional activation [], and a helix-span-helix domain in the C-terminal region, which mediates dimerisation and site-specific DNA binding [].The AP-2 family have been shown to be critical regulators of gene expression during embryogenesis. They regulate the development of facial prominence and limb buds, and are essential for cranial closure and development of the lens [, ]; they have also been implicated in tumorigenesis. AP-2 protein expression levels have been found to affect cell transformation, tumour growth and metastasis, and may predict survival in some types of cancer [, ]. Mutations in human AP-2 have been linked with bronchio-occular-facial syndrome and Char Syndrome, congenital birth defects characterised by craniofacial deformities and patent ductus arteriosus, respectively []. AP-2 gamma was originally isolated from murine carcinoma cells []. The gene was found to be expressed in several embryonic areas whose development can be affected by retinoids, such as the forebrain, face and limb buds []. A human homologue has also been identified which is involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer []. The protein was initially termed AP-2.2, but has since been reclassified as AP-2 gamma.
