Alternative titles; symbols
HGNC Approved Gene Symbol: TRIM27
Cytogenetic location: 6p22.1 Genomic coordinates (GRCh38): 6:28,903,002-28,923,985 (from NCBI)
Ret finger protein (RFP) is a DNA-binding protein associated with the nuclear matrix (Isomura et al., 1992).
Shimono et al. (2000) found that RFP interacted with EPC1 (610999) and that both proteins repressed gene transcription. Yeast 2-hybrid assays revealed that the coiled-coil domain of RFP associated with the EPcA domain and the C-terminal region of EPC. Both proteins coprecipitated from lysates of human cells and mostly colocalized in the nucleus. The coiled-coil domain of RFP and the C-terminal region of EPC1 repressed transcriptional activity in reporter gene assays, whereas the EPcA domain of EPC1 activated transcriptional activity.
Dho and Kwon (2003) transfected a human embryonic kidney cell line with RFP and observed an apoptotic response mediated by JNK (MAPK8; 601158) and p38 (MAPK14; 600289) signaling pathways originating with ASK1 (MAP3K5; 602448) and also by caspase (see CASP8; 601763) activation. RFP-induced apoptosis was independent of mitochondrial dysfunction, and the RING, B-box, and coiled-coil domains of RFP were required to induce apoptosis. Dho and Kwon (2003) concluded that RFP activates a caspase pathway independent of mitochondrial events and a stress-activated MAP kinase pathway, both of which are required for the induction of cell death.
Using a yeast 2-hybrid screen to identify proteins that affect RB1 (614041)-mediated gene activation, Krutzfeldt et al. (2005) found that RFP strongly reduced the effect of RB1 on glucocorticoid receptor (GCCR; 138040)-mediated transcription, but it did not prevent the ability of RB1 to inhibit E2F (E2F1; 189971)-mediated transcription. Mutation analysis showed that RFP interacted with the large pocket of RB1 in a manner distinct from that of E2F. Krutzfeldt et al. (2005) proposed that RFP expression may neutralize the RB1-mediated differentiation response while leaving in place E2F-dependent cell cycle regulation and apoptosis protection.
By immunoprecipitation analysis, Shimono et al. (2005) found that MCRS1 (609504) interacted with MI2-beta (CHD4; 603277), RFP, and UBF (UBTF; 600673). Yeast 2-hybrid screening showed that the central region of MCRS1 interacted with the ATPase/helicase region of MI2-beta and the coiled-coil region of RFP. Confocal microscopy demonstrated colocalization of MCRS1, MI2-beta, RFP, and UBF in nucleoli. Chromatin immunoprecipitation assays showed that MCRS1, MI2-beta, and RFP associated with rDNA and were involved in transactivation of ribosomal gene transcription, which could be downregulated by small interfering RNA-mediated downregulation of MCRS1, MI2-beta, and RFP. Shimono et al. (2005) concluded that MI2-beta and RFP, which are involved in transcriptional repression in the nucleus, associate with MCRS1 in the nucleolus and are involved in activation of rRNA transcription.
By yeast 2-hybrid screening of a B-cell cDNA library, Zha et al. (2006) found that IKKE (IKBKE; 605048) interacted with the C terminus of RFP. Coimmunoprecipitation experiments showed that RFP also interacted with TBK1 (604834), IKKA (CHUK; 600664), and IKKB (IKBKB; 603258). Immunofluorescence and confocal microscopy demonstrated primarily cytoplasmic expression of RFP and IKKE. In vitro kinase assays showed that RFP was strongly phosphorylated by IKKE and TBK1, but only weakly by IKKA and IKKB. RFP inhibited NFKB (see 164011) and interferon (see 147760)-stimulated response element activation triggered by IKK overexpression or by cytokine or viral infection pathways. Zha et al. (2006) concluded that RFP negatively regulates signaling involved in the antiviral response and inflammation by targeting IKKs.
Szpirer et al. (1997) demonstrated that although the RFP gene and a gene for an olfactory receptor (OLF89) both map to chromosome 6 less than 300 kb apart, the mouse homologs are located on 2 different chromosomes, namely 13 and 17, respectively. Thus the 2 genes delineate the breakpoint between 2 of the conserved synteny units on chromosome 6. Unit 1 (or UA) contains the major histocompatibility complex (MHC); unit 2 (or UB) contains the RFP gene. The mouse UA and UB regions are found on chromosome 17 and 13, respectively. The split at the UA/UB breakpoint must have occurred in the rodent lineage, before the mouse radiation, because the rat also shows nonsynteny of RFP and OLF89.
Dho, S. H., Kwon, K.-S. The Ret finger protein induces apoptosis via its RING finger-B box-coiled-coil motif. J. Biol. Chem. 278: 31902-31908, 2003. [PubMed: 12807881] [Full Text: https://doi.org/10.1074/jbc.M304062200]
Isomura, T., Tamiya-Koizumi, K., Suzuki, M., Yoshida, S., Taniguchi, M., Matsuyama, M., Ishigaki, T., Sakuma, S., Takahashi, M. RFP is a DNA binding protein associated with the nuclear matrix. Nucleic Acids Res. 20: 5305-5310, 1992. [PubMed: 1437549] [Full Text: https://doi.org/10.1093/nar/20.20.5305]
Krutzfeldt, M., Ellis, M., Weekes, D. B., Bull, J. J., Eilers, M., Vivanco, M. M., Sellers, W. R., Mittnacht, S. Selective ablation of retinoblastoma protein function by the RET finger protein. Molec. Cell 18: 213-224, 2005. [PubMed: 15837424] [Full Text: https://doi.org/10.1016/j.molcel.2005.03.009]
Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., Takahashi, M. Microspherule protein 1, Mi-2-beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription. J. Biol. Chem. 280: 39436-39447, 2005. [PubMed: 16186106] [Full Text: https://doi.org/10.1074/jbc.M507356200]
Shimono, Y., Murakami, H., Hasegawa, Y., Takahashi, M. RET finger protein is a transcriptional repressor and interacts with enhancer of polycomb that has dual transcriptional functions. J. Biol. Chem. 275: 39411-39419, 2000. [PubMed: 10976108] [Full Text: https://doi.org/10.1074/jbc.M006585200]
Szpirer, C., Szpirer, J., Riviere, M., Tazi, R., Pontarotti, P. Mapping of the Olf89 and Rfp genes to the rat genome: comparison with the mouse and human and new insights into the evolution of the rodent genome. Cytogenet. Cell Genet. 78: 137-139, 1997. [PubMed: 9371408] [Full Text: https://doi.org/10.1159/000134648]
Zha, J., Han, K.-J., Xu, L.-G., He, W., Zhou, Q., Chen, D., Zhai, Z., Shu, H.-B. The Ret finger protein inhibits signaling mediated by the noncanonical and canonical I-kappa-B kinase family members. J. Immun. 176: 1072-1080, 2006. [PubMed: 16393995] [Full Text: https://doi.org/10.4049/jimmunol.176.2.1072]