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Gene Review

CELF1  -  CUGBP, Elav-like family member 1

Homo sapiens

Synonyms: 50 kDa nuclear polyadenylated RNA-binding protein, BRUNOL2, Bruno-like protein 2, CELF-1, CUG triplet repeat RNA-binding protein 1, ...
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Disease relevance of CUGBP1

  • MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of myotonic dystrophy type 1 [1].
  • Accumulation of RNA CUG repeats in myotonic dystrophy type 1 (DM1) patients leads to the induction of a CUG-binding protein, CUGBP1, which increases translation of several proteins that are required for myogenesis [2].
  • EWS, an RGG-type RNA-binding protein associated with Ewing sarcoma, was identified as an interacting partner for the CUG-BP homologue in a two-hybrid assay for protein-protein interactions performed with various factors involved in RNA metabolism [3].

High impact information on CUGBP1

  • However, we observed increased levels of CUG-binding protein (CUG-BP1) in skeletal muscle, as seen in individuals with DM1 [4].
  • Altered expression of genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM pathogenesis [5].
  • CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre-messenger RNA and regulate its alternative splicing [5].
  • EDEN-BP is highly homologous to a human protein possibly involved in myotonic dystrophy [6].
  • In contrast, increasing the levels of CUGBP1 worsens (iCUG)480-induced degeneration even though CUGBP1 distribution is not altered by the expression of the expanded triplet repeat [1].

Biological context of CUGBP1

  • We also report that altering the levels of two RNA-BP known to be involved in DM1 pathogenesis, MBNL1 and CUGBP1, modify the (iCUG)480 degenerative phenotypes [1].
  • It was previously shown that delay of muscle differentiation and insulin resistance in DM1 are associated with misregulation of CUGBP1 protein levels [7].
  • We previously identified an RNA binding protein, CUGBP1, which binds to GCN repeats located within the 5' region of C/EBPbeta mRNAs and regulates translation of C/EBPbeta isoforms [8].
  • Failure of DM cells to accumulate CUGBP1 in the cytoplasm leads to a significant reduction of p21 and to alterations of other proteins responsible for the cell cycle withdrawal [9].
  • Several lines of evidence show that CUGBP1 induces the translation of p21 via binding to a GC-rich sequence located within the 5' region of p21 mRNA [9].

Anatomical context of CUGBP1

  • Two HeLa cell proteins, CUG-BP1 and CUG-BP2, have been purified based upon their ability to bind specifically to (CUG)8 oligonucleotides in vitro [10].
  • Skeletal muscle cells from DM patients fail to induce cytoplasmic levels of a CUG RNA binding protein, CUGBP1, while normal differentiated cells accumulate CUGBP1 in the cytoplasm [9].
  • Our data provide evidence for an impaired cell cycle withdrawal in DM muscle cells and suggest that alterations in the activity of CUGBP1 causes disruption of p21-dependent control of cell cycle arrest [9].
  • Similarly to DM patients, overexpression of RNA CUG repeats in cultured cells results in the re-allocation of CUGBP1 from a free state to the RNA.protein complexes containing CUG repeats [11].
  • Analysis of cytoplasmic and polysomal proteins from rat liver after PH showed that CUGBP1 is associated with polysomes that translate low molecular weight isoforms of C/EBPbeta [12].

Associations of CUGBP1 with chemical compounds

  • Experiments with cyclohexamide-dependent block of protein synthesis showed that the half-life of CUGBP1 is increased in cells expressing CUG repeats [11].
  • Tumor necrosis factor-alpha, levels of which are elevated in fat tissue with aging, increased CUGBP1 protein, CUGBP1 binding activity, and C/EBPbeta-LIP in preadipocytes from young rats [13].

Physical interactions of CUGBP1


Enzymatic interactions of CUGBP1


Other interactions of CUGBP1

  • Our data demonstrate that both CUGBP1 and CRT interact with GCU repeats within myotonin protein kinase and with GCN repeats within C/EBPalpha and C/EBPbeta mRNAs [8].
  • The CUGBP1 mRNA was found to contain several CAG repeat sequences [16].
  • In vitro RNA-RNA binding experiments demonstrated that the incubation of expanded CUG repeats with CUGBP1 RNA generated a higher molecular weight band, which was digested by RNase III [16].
  • CUG-BP1 is thus a previously unidentified downstream target of EGFR signaling and represents a new translational regulator of LIP expression in human mammary epithelial cells [17].
  • These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex [18].

Analytical, diagnostic and therapeutic context of CUGBP1

  • In addition, a semi-quantitative RT-PCR assay showed that the relative amount of CUGBP1 mRNA was reduced in muscle biopsy samples from 10 DM1 patients compared to that from five normal individuals (P < 0.01) and 10 myopathic disease controls (P < 0.01) [16].
  • Northern blot analysis demonstrated that the quantity of CUGBP1 mRNA in three DM1 patients was approximately 70% of that observed in three normal controls (P < 0.05) [16].
  • Using electron microscopy, we visualized large RNAs containing up to 130 CUG repeats and studied the binding of purified CUG-binding protein (CUG-BP) to these RNAs [19].
  • Surface plasmon resonance and electrophoretic mobility-shift assays showed that these two families differed in their ability to bind CUG-BP1 [20].
  • Using a combination of indirect immunofluorescence to detect endogenous proteins and overexpression of proteins with green fluorescent protein (GFP) tags we have shown that CUG-BP and hnRNP C do not co-localise with expanded repeat foci in DM1 cell lines [21].


  1. MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of myotonic dystrophy type 1. de Haro, M., Al-Ramahi, I., De Gouyon, B., Ukani, L., Rosa, A., Faustino, N.A., Ashizawa, T., Cooper, T.A., Botas, J. Hum. Mol. Genet. (2006) [Pubmed]
  2. Overexpression of CUG triplet repeat-binding protein, CUGBP1, in mice inhibits myogenesis. Timchenko, N.A., Patel, R., Iakova, P., Cai, Z.J., Quan, L., Timchenko, L.T. J. Biol. Chem. (2004) [Pubmed]
  3. A trans-acting factor, isolated by the three-hybrid system, that influences alternative splicing of the amyloid precursor protein minigene. Poleev, A., Hartmann, A., Stamm, S. Eur. J. Biochem. (2000) [Pubmed]
  4. Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy. Mahadevan, M.S., Yadava, R.S., Yu, Q., Balijepalli, S., Frenzel-McCardell, C.D., Bourne, T.D., Phillips, L.H. Nat. Genet. (2006) [Pubmed]
  5. Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Philips, A.V., Timchenko, L.T., Cooper, T.A. Science (1998) [Pubmed]
  6. EDEN and EDEN-BP, a cis element and an associated factor that mediate sequence-specific mRNA deadenylation in Xenopus embryos. Paillard, L., Omilli, F., Legagneux, V., Bassez, T., Maniey, D., Osborne, H.B. EMBO J. (1998) [Pubmed]
  7. Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions. Furling, D., Doucet, G., Langlois, M.A., Timchenko, L., Belanger, E., Cossette, L., Puymirat, J. Gene Ther. (2003) [Pubmed]
  8. Calreticulin interacts with C/EBPalpha and C/EBPbeta mRNAs and represses translation of C/EBP proteins. Timchenko, L.T., Iakova, P., Welm, A.L., Cai, Z.J., Timchenko, N.A. Mol. Cell. Biol. (2002) [Pubmed]
  9. Molecular basis for impaired muscle differentiation in myotonic dystrophy. Timchenko, N.A., Iakova, P., Cai, Z.J., Smith, J.R., Timchenko, L.T. Mol. Cell. Biol. (2001) [Pubmed]
  10. Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Timchenko, L.T., Miller, J.W., Timchenko, N.A., DeVore, D.R., Datar, K.V., Lin, L., Roberts, R., Caskey, C.T., Swanson, M.S. Nucleic Acids Res. (1996) [Pubmed]
  11. RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1. Timchenko, N.A., Cai, Z.J., Welm, A.L., Reddy, S., Ashizawa, T., Timchenko, L.T. J. Biol. Chem. (2001) [Pubmed]
  12. CUG repeat binding protein (CUGBP1) interacts with the 5' region of C/EBPbeta mRNA and regulates translation of C/EBPbeta isoforms. Timchenko, N.A., Welm, A.L., Lu, X., Timchenko, L.T. Nucleic Acids Res. (1999) [Pubmed]
  13. Increased CUG triplet repeat-binding protein-1 predisposes to impaired adipogenesis with aging. Karagiannides, I., Thomou, T., Tchkonia, T., Pirtskhalava, T., Kypreos, K.E., Cartwright, A., Dalagiorgou, G., Lash, T.L., Farmer, S.R., Timchenko, N.A., Kirkland, J.L. J. Biol. Chem. (2006) [Pubmed]
  14. CUG-BP binds to RNA substrates and recruits PARN deadenylase. Moraes, K.C., Wilusz, C.J., Wilusz, J. RNA (2006) [Pubmed]
  15. Altered phosphorylation and intracellular distribution of a (CUG)n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice. Roberts, R., Timchenko, N.A., Miller, J.W., Reddy, S., Caskey, C.T., Swanson, M.S., Timchenko, L.T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  16. Altered expression of CUG binding protein 1 mRNA in myotonic dystrophy 1: possible RNA-RNA interaction. Watanabe, T., Takagi, A., Sasagawa, N., Ishiura, S., Nakase, H. Neurosci. Res. (2004) [Pubmed]
  17. Epidermal growth factor receptor stimulation activates the RNA binding protein CUG-BP1 and increases expression of C/EBPbeta-LIP in mammary epithelial cells. Baldwin, B.R., Timchenko, N.A., Zahnow, C.A. Mol. Cell. Biol. (2004) [Pubmed]
  18. Age-specific CUGBP1-eIF2 Complex Increases Translation of CCAAT/Enhancer-binding Protein beta in Old Liver. Timchenko, L.T., Salisbury, E., Wang, G.L., Nguyen, H., Albrecht, J.H., Hershey, J.W., Timchenko, N.A. J. Biol. Chem. (2006) [Pubmed]
  19. Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein. Michalowski, S., Miller, J.W., Urbinati, C.R., Paliouras, M., Swanson, M.S., Griffith, J. Nucleic Acids Res. (1999) [Pubmed]
  20. CUG-BP1/CELF1 requires UGU-rich sequences for high-affinity binding. Marquis, J., Paillard, L., Audic, Y., Cosson, B., Danos, O., Le Bec, C., Osborne, H.B. Biochem. J. (2006) [Pubmed]
  21. In vivo co-localisation of MBNL protein with DMPK expanded-repeat transcripts. Fardaei, M., Larkin, K., Brook, J.D., Hamshere, M.G. Nucleic Acids Res. (2001) [Pubmed]
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