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Gene Review

Frat1  -  frequently rearranged in advanced T cell...

Mus musculus

Synonyms: AW060382, FRAT-1, Frequently rearranged in advanced T-cell lymphomas 1, Proto-oncogene FRAT1
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Disease relevance of Frat1


High impact information on Frat1


Biological context of Frat1

  • Frat2 protein accumulates to higher levels upon transfection into 293T cells than either Frat1 or Frat3 [1].
  • Frat1 and Frat2 are juxtaposed on chromosome 19 in a chromosomal organization conserved between man and mouse [1].
  • We show that Frat1 and Frat2 are phosphorylated, which is the first evidence that these proteins are subject to posttranslational modification [1].
  • In an attempt to gain more insight into the function of Frat1, we have generated Frat1-deficient mice in which most of the coding domain was replaced by a promoterless beta-galactosidase reporter gene [6].
  • The overlapping expression patterns of Frat1 and Frat3 during murine embryogenesis suggest that the apparent dispensability of Frat1 for proper development may be due to the presence of a second mouse gene encoding a functional Frat protein [6].

Anatomical context of Frat1


Other interactions of Frat1

  • This analysis revealed that Lvis1 maps between two previously identified viral insertion sites, His2 and Frat1, and does not cosegregate with known gene markers [7].
  • Together these data suggest that Frat may be the endogenous factor that targets GSK-3 for nuclear export [8].
  • Axin, which has been shown to interact with LRP5 and to be recruited to the membrane through this interaction, was found to co-immunoprecipitate with Frat1 and LRP5 [5].
  • Contrary to most common insertion sites implicated in mouse T cell lymphomagenesis, retroviral insertional mutagenesis of Frat1 constitutes a relatively late event in M-MuLV-induced tumor development, suggesting that proviral activation of Frat1 contributes to progression of T cell lymphomas rather than their genesis [3].

Analytical, diagnostic and therapeutic context of Frat1

  • Molecular cloning of common proviral insertion sites that were detected preferentially in transplanted tumors led to the identification of a novel gene, designated Frat1 [2].
  • Transplantation of such primary lymphomas allows for a further expansion of tumor cell clones carrying a proviral insertion near Frat1, resulting in detectable Frat1 rearrangements in 17% of the transplanted E mu-Pim1 tumors and 30% of the transplanted H2-K-myc tumors, respectively [2].


  1. Characterization and functional analysis of the murine Frat2 gene. van Amerongen, R., van der Gulden, H., Bleeker, F., Jonkers, J., Berns, A. J. Biol. Chem. (2004) [Pubmed]
  2. Activation of a novel proto-oncogene, Frat1, contributes to progression of mouse T-cell lymphomas. Jonkers, J., Korswagen, H.C., Acton, D., Breuer, M., Berns, A. EMBO J. (1997) [Pubmed]
  3. Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression. Jonkers, J., Weening, J.J., van der Valk, M., Bobeldijk, R., Berns, A. Oncogene (1999) [Pubmed]
  4. Identification and characterization of collaborating oncogenes in compound mutant mice. Berns, A., Mikkers, H., Krimpenfort, P., Allen, J., Scheijen, B., Jonkers, J. Cancer Res. (1999) [Pubmed]
  5. Interaction between LRP5 and Frat1 mediates the activation of the Wnt canonical pathway. Hay, E., Faucheu, C., Suc-Royer, I., Touitou, R., Stiot, V., Vayssière, B., Baron, R., Roman-Roman, S., Rawadi, G. J. Biol. Chem. (2005) [Pubmed]
  6. In vivo analysis of Frat1 deficiency suggests compensatory activity of Frat3. Jonkers, J., van Amerongen, R., van der Valk, M., Robanus-Maandag, E., Molenaar, M., Destrée, O., Berns, A. Mech. Dev. (1999) [Pubmed]
  7. A mouse chromosome 19 genetic map including the Lvis1 viral insertion site. Hansen, G.M., Tackles, D., Schwartz, C., Justice, M.J. Genomics (1999) [Pubmed]
  8. The regulation of glycogen synthase kinase-3 nuclear export by Frat/GBP. Franca-Koh, J., Yeo, M., Fraser, E., Young, N., Dale, T.C. J. Biol. Chem. (2002) [Pubmed]
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