RFP represses transcriptional activation by bHLH transcription factors

Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Hills Road, Cambridge CB2 2XY, UK.
Oncogene (Impact Factor: 8.46). 11/2005; 24(45):6729-36. DOI: 10.1038/sj.onc.1208828
Source: PubMed


Basic helix-loop-helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins initially identified as a recombined transforming gene from a human lymphoma, is a novel interaction partner for four different bHLH proteins (SCL, E47, MyoD and mASH-1), but does not interact with GATA-1 or PU.1. Interaction with SCL required the B-box and first coiled-coil region of RFP together with the bHLH domain of SCL. RFP was able to repress transcriptional activation by E47, MyoD and mASH-1, but not by members of several other transcription factor families. Transcriptional repression by RFP was trichostatin A sensitive and did not involve an Id-like mechanism or ubiquitination with subsequent degradation of bHLH proteins. Instead, our results suggest that bHLH transcription factors are regulated by a previously undescribed interaction with RFP, which functions to recruit HDAC and/or Polycomb proteins and thus repress target genes of bHLH proteins. These results reveal an unexpected link between the bHLH and TRIM protein families.

Download full-text


Available from: Ekaterini Kotsopoulou, Jul 09, 2015
  • Source
    • "Furthermore, interaction with members of the protein inhibitors of activated STAT (PIAS) family results in targeting of TRIM27 to subnuclear compartments by TRIM27 SUMOylation [33]. A role for TRIM27 in transcriptional repression [34], [35], the negative regulation of NF-κB and IFN-signaling pathways [36], apoptosis [37], and in cell cycle regulation [38] has been reported, suggesting that TRIM27 is involved in the control of multiple cellular processes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses. Dysfunctional NOD2 activity can lead to severe inflammatory disorders, but the regulation of NOD2 is still poorly understood. Recently, proteins of the tripartite motif (TRIM) protein family have emerged as regulators of innate immune responses by acting as E3 ubiquitin ligases. We identified TRIM27 as a new specific binding partner for NOD2. We show that NOD2 physically interacts with TRIM27 via the nucleotide-binding domain, and that NOD2 activation enhances this interaction. Dependent on functional TRIM27, ectopically expressed NOD2 is ubiquitinated with K48-linked ubiquitin chains followed by proteasomal degradation. Accordingly, TRIM27 affects NOD2-mediated pro-inflammatory responses. NOD2 mutations are linked to susceptibility to Crohn's disease. We found that TRIM27 expression is increased in Crohn's disease patients, underscoring a physiological role of TRIM27 in regulating NOD2 signaling. In HeLa cells, TRIM27 is partially localized in the nucleus. We revealed that ectopically expressed NOD2 can shuttle to the nucleus in a Walker A dependent manner, suggesting that NOD2 and TRIM27 might functionally cooperate in the nucleus. We conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.
    Full-text · Article · Jul 2012 · PLoS ONE
  • Source
    • "In somatic cells, SUMO-I modification of RFP induces its relocalization into nuclear bodies reminiscent of the PML bodies and strengthens its transcriptional repressor activity [7]. RFP has also been proposed to repress transcriptional activity of specific proteins such as Retinoblastoma protein or bHLH transcription factors [17] [18]. However, the role of RFP in meiotic cells remains unclear. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During prophase I of male meiosis, the sex chromosomes form a compact structure called XY body that associates with the nuclear membrane of pachytene spermatocytes. Ret Finger Protein is a transcriptional repressor, able to interact with both nuclear matrix-associated proteins and double-stranded DNA. We report the precise and unique localization of Ret Finger Protein in pachytene spermatocytes, in which Ret Finger Protein takes place of lamin B1, between the XY body and the inner nuclear membrane. This localization of Ret Finger Protein does not seem to be associated with O-glycosylation or sumoylation. In addition, we demonstrate that Ret Finger Protein contains an E3 ubiquitin ligase activity. These observations lead to an attractive hypothesis in which Ret Finger Protein would be involved in the positioning and the attachment of XY body to the nuclear lamina of pachytene spermatocytes.
    Full-text · Article · Dec 2009 · International Journal of Cell Biology
  • Source
    • "Of these, several are implicated in cancers and disease states such as breast cancer (Urano et al., 2002), lymphoma (Kosaka et al., 2007), specific forms of muscular dystrophy (Kudryashova et al., 2005) and Opitz syndrome (Cho et al., 2006) and see (Meroni and Diez-Roux, 2005). TRIM proteins are found in all metazoans where they function in a diverse array of cellular processes such as apoptosis, proliferation, differentiation and immune response (Evans et al., 2004; Bloor et al., 2005; Meroni and Diez-Roux, 2005; Lee et al., 2006). Potentially, this diversification of function partially reflects the RING domains E3 ligase activity. "

    Preview · Article ·
Show more