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Gene Review

TFEB  -  transcription factor EB

Homo sapiens

Synonyms: ALPHATFEB, BHLHE35, Class E basic helix-loop-helix protein 35, TCFEB, Transcription factor EB, ...
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Disease relevance of TFEB


High impact information on TFEB

  • Binding by TFEB and TFE3 to related, but different, naturally occurring DNA target sequences was observed with distinct binding preferences [3].
  • TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family [3].
  • In two primary tumors we found that Alpha, an intronless gene, rearranges with the first intron of TFEB, just upstream of TFEB's initiation ATG, preserving the entire TFEB coding sequence [2].
  • Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation [2].
  • We describe the rational design of a DNA-binding antibody, Fab-Ebox, by replacing a variable segment of the immunoglobulin heavy chain with a 17-amino acid domain derived from TFEB, a class B basic helix-loop-helix protein [5].

Chemical compound and disease context of TFEB

  • A highly distinctive subset of renal neoplasms of children and young adults contains a t(6;11)(p21;q12), a translocation recently been shown to result in fusion of Alpha, a gene on 11q12, with the transcription factor gene TFEB on 6p21 [4].
  • Using a polyclonal antibody to TFEB on formalin-fixed, paraffin-embedded tissue sections, we found that all 7 renal neoplasms with the t(6;11) demonstrated moderate (2 cases) or strong (5 cases) nuclear TFEB immunoreactivity [4].

Biological context of TFEB


Anatomical context of TFEB


Associations of TFEB with chemical compounds

  • Fluorescence in situ hybridization confirmed the involvement of both TFEB and Alpha in this translocation [2].
  • Based on these results we conclude that the RCC-associated t(6;11)(p21;q13) translocation leads to a dramatic transcriptional and translational upregulation of TFEB due to promoter substitution, thereby severely unbalancing the nuclear ratios of the MITF/TFE subfamily members [1].
  • Comparable interference of binding by methylation of cytosine residues indicated that Fab-Ebox and TFEB both contact DNA through interactions along the major groove of double-stranded DNA [5].
  • The dimerization stability of the HLH-LZ transcription protein family is modulated by the leucine zippers: a CD and NMR study of TFEB and c-Myc [10].
  • Comparison of the Delta V values for these ethers with those of the previously studied(37-39) monolayers of trifluoroethyl ester (TFEB) and ethyl ester of behenic acid (EB) shows that the reversal of the sign of Delta V causes the same change Delta(Delta V) = -706 +/- 16 mV due to fluorination of heads [11].

Other interactions of TFEB

  • Translocation RCC, bearing TFE3 or TFEB gene fusions, are recently recognized entities for which risk factors have not been identified [12].
  • We found that, similar to the MiTF gene, the genes for TFEB and TFEC contain multiple alternative first exons with restricted and differential tissue distributions [6].
  • The DNA-binding factor TFEB contains adjacent helix-loop-helix (HLH) and leucine zipper (LZ) domains flanked by an upstream basic region [3].
  • The TFEB protein is known to form homodimers. c-Myc, on the other hand, does not homodimerize in vivo, but is mostly found in heterodimeric complexes with Max, another protein of the HLH-LZ family [10].

Analytical, diagnostic and therapeutic context of TFEB


  1. Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution. Kuiper, R.P., Schepens, M., Thijssen, J., van Asseldonk, M., van den Berg, E., Bridge, J., Schuuring, E., Schoenmakers, E.F., van Kessel, A.G. Hum. Mol. Genet. (2003) [Pubmed]
  2. Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. Davis, I.J., Hsi, B.L., Arroyo, J.D., Vargas, S.O., Yeh, Y.A., Motyckova, G., Valencia, P., Perez-Atayde, A.R., Argani, P., Ladanyi, M., Fletcher, J.A., Fisher, D.E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family. Fisher, D.E., Carr, C.S., Parent, L.A., Sharp, P.A. Genes Dev. (1991) [Pubmed]
  4. Renal carcinomas with the t(6;11)(p21;q12): clinicopathologic features and demonstration of the specific alpha-TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA PCR. Argani, P., Laé, M., Hutchinson, B., Reuter, V.E., Collins, M.H., Perentesis, J., Tomaszewski, J.E., Brooks, J.S., Acs, G., Bridge, J.A., Vargas, S.O., Davis, I.J., Fisher, D.E., Ladanyi, M. Am. J. Surg. Pathol. (2005) [Pubmed]
  5. Transplantation of a 17-amino acid alpha-helical DNA-binding domain into an antibody molecule confers sequence-dependent DNA recognition. McLane, K.E., Burton, D.R., Ghazal, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  6. Regulation of the MiTF/TFE bHLH-LZ transcription factors through restricted spatial expression and alternative splicing of functional domains. Kuiper, R.P., Schepens, M., Thijssen, J., Schoenmakers, E.F., van Kessel, A.G. Nucleic Acids Res. (2004) [Pubmed]
  7. A helix-loop-helix protein related to the immunoglobulin E box-binding proteins. Carr, C.S., Sharp, P.A. Mol. Cell. Biol. (1990) [Pubmed]
  8. Sumoylation of MITF and its related family members TFE3 and TFEB. Miller, A.J., Levy, C., Davis, I.J., Razin, E., Fisher, D.E. J. Biol. Chem. (2005) [Pubmed]
  9. Renal carcinoma-associated transcription factors TFE3 and TFEB are leukemia inhibitory factor-responsive transcription activators of E-cadherin. Huan, C., Sashital, D., Hailemariam, T., Kelly, M.L., Roman, C.A. J. Biol. Chem. (2005) [Pubmed]
  10. The dimerization stability of the HLH-LZ transcription protein family is modulated by the leucine zippers: a CD and NMR study of TFEB and c-Myc. Muhle-Goll, C., Gibson, T., Schuck, P., Schubert, D., Nalis, D., Nilges, M., Pastore, A. Biochemistry (1994) [Pubmed]
  11. Negative dipole potentials of uncharged langmuir monolayers due to fluorination of the hydrophilic heads. Petrov, J.G., Andreeva, T.D., Kurth, D.G., Möhwald, H. The journal of physical chemistry. B, Condensed matter, materials, surfaces, interfaces & biophysical. (2005) [Pubmed]
  12. Translocation carcinomas of the kidney after chemotherapy in childhood. Argani, P., Laé, M., Ballard, E.T., Amin, M., Manivel, C., Hutchinson, B., Reuter, V.E., Ladanyi, M. J. Clin. Oncol. (2006) [Pubmed]
  13. Translocation carcinomas of the kidney. Argani, P., Ladanyi, M. Clin. Lab. Med. (2005) [Pubmed]
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