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Gene Review

Dtx1  -  deltex 1 homolog (Drosophila)

Mus musculus

Synonyms: Deltex1, E3 ubiquitin-protein ligase DTX1, FXI-T1, Fxit1, Protein deltex-1, ...
 
 
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Disease relevance of Dtx1

  • A novel cDNA transcript, FX-induced transcript 1 (FXI-T1), showed strong differential mRNA expression in all C57BL/6 FX-induced thymomas examined when compared with normal thymus tissue [1].
 

High impact information on Dtx1

  • Notch activation occurs early in tumorigenesis and may precede transformation, as ectopic expression of the Notch targets Hes-1 and Deltex-1 is detected in thymocytes from young Ik(L/L) mice with no overt signs of transformation [2].
  • T Cells Develop Normally in the Absence of both Deltex1 and Deltex2 [3].
  • Its pattern of lymphoid expression as well as gain-of-function experiments suggest that Deltex-1 regulates both B-cell lineage and splenic marginal-zone B-cell commitment [4].
  • Normal immune system development in mice lacking the Deltex-1 RING finger domain [4].
  • Deltex-1 was also found to be highly expressed in germinal-center B cells [4].
 

Biological context of Dtx1

 

Anatomical context of Dtx1

 

Associations of Dtx1 with chemical compounds

  • Neither treatment with combined (alpha CD3)/(alpha CD28) antibodies nor the combination of the phorbol ester PMA and calcium ionophore ionomycin affects expression of Deltex in immature thymocytes; however, PMA/ionomycin treatment does downregulate expression of HES-1, an affect mostly mediated by ionomycin [10].
 

Regulatory relationships of Dtx1

  • We further found that Deltex promoted degradation of the C-terminal catalytic fragment of MEKK1 [MEKK1(C)] [6].
 

Other interactions of Dtx1

  • Our results reveal a novel mechanism as to how Deltex selectively suppresses T-cell activation through degradation of a key signaling molecule, MEKK1 [6].
  • Therefore, MEKK1(C), the dominant form of MEKK1 in T cells, is a target of Deltex E3 ubiquitin ligase [6].
 

Analytical, diagnostic and therapeutic context of Dtx1

  • Using a semiquantitative RTPCR approach, we show that both Deltex and HES-1 transcriptional levels are developmentally regulated as thymocytes mature from the earliest CD4/CD8 double negative thymocyte stage, through the intermediate CD4/CD8 double positive stage, and finally to the mature CD4 or CD8 single positive stage [10].

References

  1. A novel cDNA transcript expressed in fractionated X-irradiation-induced murine thymomas. Pampeno, C.L., Meruelo, D. Cell Growth Differ. (1996) [Pubmed]
  2. Notch activation is an early and critical event during T-Cell leukemogenesis in Ikaros-deficient mice. Dumortier, A., Jeannet, R., Kirstetter, P., Kleinmann, E., Sellars, M., dos Santos, N.R., Thibault, C., Barths, J., Ghysdael, J., Punt, J.A., Kastner, P., Chan, S. Mol. Cell. Biol. (2006) [Pubmed]
  3. T Cells Develop Normally in the Absence of both Deltex1 and Deltex2. Lehar, S.M., Bevan, M.J. Mol. Cell. Biol. (2006) [Pubmed]
  4. Normal immune system development in mice lacking the Deltex-1 RING finger domain. Storck, S., Delbos, F., Stadler, N., Thirion-Delalande, C., Bernex, F., Verthuy, C., Ferrier, P., Weill, J.C., Reynaud, C.A. Mol. Cell. Biol. (2005) [Pubmed]
  5. Expression of Deltex1 during mouse embryogenesis: comparison with Notch1, 2 and 3 expression. Mitsiadis, T.A., Gayet, O., Zhang, N., Carroll, P. Mech. Dev. (2001) [Pubmed]
  6. Deltex regulates T-cell activation by targeted degradation of active MEKK1. Liu, W.H., Lai, M.Z. Mol. Cell. Biol. (2005) [Pubmed]
  7. Genomic analysis and localization of murine Deltex, a modulator of notch activity, to mouse chromosome 5 and its human homolog to chromosome 12. Pampeno, C.L., Vallerie, A.M., Choi, J., Meruelo, N.C., Meruelo, D. DNA Cell Biol. (2001) [Pubmed]
  8. Notch1 signaling regulates radial glia differentiation through multiple transcriptional mechanisms. Patten, B.A., Sardi, S.P., Koirala, S., Nakafuku, M., Corfas, G. J. Neurosci. (2006) [Pubmed]
  9. NB-3/Notch1 pathway via Deltex1 promotes neural progenitor cell differentiation into oligodendrocytes. Cui, X.Y., Hu, Q.D., Tekaya, M., Shimoda, Y., Ang, B.T., Nie, D.Y., Sun, L., Hu, W.P., Karsak, M., Duka, T., Takeda, Y., Ou, L.Y., Dawe, G.S., Yu, F.G., Ahmed, S., Jin, L.H., Schachner, M., Watanabe, K., Arsenijevic, Y., Xiao, Z.C. J. Biol. Chem. (2004) [Pubmed]
  10. Characterization of the transcriptional expression of Notch-1 signaling pathway members, Deltex and HES-1, in developing mouse thymocytes. Choi, J.W., Pampeno, C., Vukmanovic, S., Meruelo, D. Dev. Comp. Immunol. (2002) [Pubmed]
 
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