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Gene Review

ttk  -  tramtrack

Drosophila melanogaster

Synonyms: 0037/17, 0250/25, 0438/31, 0702/07, 1049/07, ...
 
 
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Disease relevance of ttk

 

High impact information on ttk

  • The initial establishment of repression is sensitive to the dosage of the zinc-finger transcription factor Tramtrack [2].
  • We show that Sevenless activates prospero independent of the enhancer and involves targeted degradation of Tramtrack, a transcription repressor [3].
  • Phyllopod (PHYL) acts to antagonize this repression by a mechanism that requires Seven In Absentia (SINA) and is associated with decreased TTK88 protein levels, but not reduced ttk88 gene transcription or mRNA stability [4].
  • PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism [4].
  • The transcription repressor Tramtrack (TTK) is found in cone cells but not photoreceptor cells of the Drosophila eye [5].
 

Biological context of ttk

  • An additional ttk-related cDNA clone was isolated which gives rise to an 88 kDa protein with an alternative set of zinc fingers having a DNA binding specificity distinct from that of the 69 kDa protein [6].
  • Both proteins were shown to be encoded by the ttk gene through alternative splicing, providing the first example of the use of this mechanism to generate related proteins with distinct DNA binding specificities [6].
  • Pointed and Tramtrack69 establish an EGFR-dependent transcriptional switch to regulate mitosis [7].
  • We report the identification of a mutation in the Drosophila tramtrack (ttk) locus that is required for cell fate determination in the compound eye. ttk is expressed as two proteins, p69 and p88, shown previously to bind to the regulatory regions of several segmentation genes [8].
  • Fringe-dependent notch activation and tramtrack function are required for specification of the polar cells in Drosophila oogenesis [9].
 

Anatomical context of ttk

  • One of the Drosophila sequences, ttk, is a developmental control gene, while a second does not contain a zinc finger region but encodes a structure important in oocyte development [10].
  • I propose that Tramtrack ensures stable mature glial identity by both repressing neuroblast-specific genes and controlling glial cell proliferation [11].
  • When expressed ectopically before neural stem cell formation, Tramtrack represses the neural stem cell-specific genes asense and deadpan [11].
  • Complementation analyses, immunolocalization, and rescue data demonstrate that these defects are due to loss of Ttk69, which is expressed in the follicle cells and is required for normal chorion production and dorsal follicle-cell migration [12].
  • The screen also identified the genes couch potato and tramtrack, previously known from their roles in peripheral nervous system development, as being expressed in the ring gland [13].
 

Physical interactions of ttk

  • The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern [14].
  • A dCtBP consensus binding motif in the C terminus appears to contribute to Ttk69 activity, but it cannot be fully responsible for the function of the C terminus [15].
  • Here we report that Sequoia is a pan-neural nuclear protein containing two putative zinc fingers homologous to the DNA binding domain of Tramtrack. sequoia mutants affect the cell fate decision of a small subset of neurons but have global effects on axon and dendrite morphologies of most and possibly all neurons [16].
 

Enzymatic interactions of ttk

 

Regulatory relationships of ttk

  • Notch signaling through tramtrack bypasses the mitosis promoting activity of the JNK pathway in the mitotic-to-endocycle transition of Drosophila follicle cells [18].
  • Here we present evidence that the 69-kDa ttk protein can indeed repress expression not only of ftz, but also of eve [19].
  • Musashi and seven in absentia downregulate Tramtrack through distinct mechanisms in Drosophila eye development [20].
  • These studies reveal that DNA-binding proteins encoded by the tramtrack locus cooperate with Runt to repress engrailed [21].
  • Reduction of either yan or ttk activity suppresses eye phenotypes of the kinase suppressor of ras (ksr) gene mutation, which is consistent with the involvement of yan and ttk in the Ras/MAPK pathway [22].
 

Other interactions of ttk

  • We have observed that the transcription of several genes, including ftz, is triggered in embryos at a critical nuclear density; therefore, we suggest that titration of transcription factors like ttk by the nucleocytoplasmic ratio triggers zygotic transcription in Drosophila [23].
  • Here we show that two antagonistic transcriptional regulators, Pointed, an activator, and Tramtrack69, a repressor, directly regulate the transcription of string [7].
  • In addition, a downstream target of Notch, tramtrack, acts at the mitotic-to-endocycle transition [18].
  • This leads to Ttk expression in the daughter cell that does not inherit Numb [24].
  • Tramtrack69 is required for the early repression of tailless expression [25].
 

Analytical, diagnostic and therapeutic context of ttk

References

  1. Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain. Soltysik-Espanola, M., Rogers, R.A., Jiang, S., Kim, T.A., Gaedigk, R., White, R.A., Avraham, H., Avraham, S. Mol. Biol. Cell (1999) [Pubmed]
  2. Distinct in vivo requirements for establishment versus maintenance of transcriptional repression. Wheeler, J.C., VanderZwan, C., Xu, X., Swantek, D., Tracey, W.D., Gergen, J.P. Nat. Genet. (2002) [Pubmed]
  3. Overlapping activators and repressors delimit transcriptional response to receptor tyrosine kinase signals in the Drosophila eye. Xu, C., Kauffmann, R.C., Zhang, J., Kladny, S., Carthew, R.W. Cell (2000) [Pubmed]
  4. PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism. Tang, A.H., Neufeld, T.P., Kwan, E., Rubin, G.M. Cell (1997) [Pubmed]
  5. Photoreceptor cell differentiation requires regulated proteolysis of the transcriptional repressor Tramtrack. Li, S., Li, Y., Carthew, R.W., Lai, Z.C. Cell (1997) [Pubmed]
  6. Alternatively spliced transcripts of the Drosophila tramtrack gene encode zinc finger proteins with distinct DNA binding specificities. Read, D., Manley, J.L. EMBO J. (1992) [Pubmed]
  7. Pointed and Tramtrack69 establish an EGFR-dependent transcriptional switch to regulate mitosis. Baonza, A., Murawsky, C.M., Travers, A.A., Freeman, M. Nat. Cell Biol. (2002) [Pubmed]
  8. tramtrack is a transcriptional repressor required for cell fate determination in the Drosophila eye. Xiong, W.C., Montell, C. Genes Dev. (1993) [Pubmed]
  9. Fringe-dependent notch activation and tramtrack function are required for specification of the polar cells in Drosophila oogenesis. Althauser, C., Jordan, K.C., Deng, W.M., Ruohola-Baker, H. Dev. Dyn. (2005) [Pubmed]
  10. A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein. Sugawara, M., Scholl, T., Ponath, P.D., Strominger, J.L. Mol. Cell. Biol. (1994) [Pubmed]
  11. Tramtrack controls glial number and identity in the Drosophila embryonic CNS. Badenhorst, P. Development (2001) [Pubmed]
  12. The Drosophila female sterile mutation twin peaks is a novel allele of tramtrack and reveals a requirement for Ttk69 in epithelial morphogenesis. French, R.L., Cosand, K.A., Berg, C.A. Dev. Biol. (2003) [Pubmed]
  13. Genes expressed in the ring gland, the major endocrine organ of Drosophila melanogaster. Harvie, P.D., Filippova, M., Bryant, P.J. Genetics (1998) [Pubmed]
  14. The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern. Harrison, S.D., Travers, A.A. EMBO J. (1990) [Pubmed]
  15. The N-terminal BTB/POZ domain and C-terminal sequences are essential for Tramtrack69 to specify cell fate in the developing Drosophila eye. Wen, Y., Nguyen, D., Li, Y., Lai, Z.C. Genetics (2000) [Pubmed]
  16. Sequoia, a tramtrack-related zinc finger protein, functions as a pan-neural regulator for dendrite and axon morphogenesis in Drosophila. Brenman, J.E., Gao, F.B., Jan, L.Y., Jan, Y.N. Dev. Cell (2001) [Pubmed]
  17. The bereft gene, a potential target of the neural selector gene cut, contributes to bristle morphogenesis. Hardiman, K.E., Brewster, R., Khan, S.M., Deo, M., Bodmer, R. Genetics (2002) [Pubmed]
  18. Notch signaling through tramtrack bypasses the mitosis promoting activity of the JNK pathway in the mitotic-to-endocycle transition of Drosophila follicle cells. Jordan, K.C., Schaeffer, V., Fischer, K.A., Gray, E.E., Ruohola-Baker, H. BMC Dev. Biol. (2006) [Pubmed]
  19. Ectopic expression of the Drosophila tramtrack gene results in multiple embryonic defects, including repression of even-skipped and fushi tarazu. Read, D., Levine, M., Manley, J.L. Mech. Dev. (1992) [Pubmed]
  20. Musashi and seven in absentia downregulate Tramtrack through distinct mechanisms in Drosophila eye development. Hirota, Y., Okabe, M., Imai, T., Kurusu, M., Yamamoto, A., Miyao, S., Nakamura, M., Sawamoto, K., Okano, H. Mech. Dev. (1999) [Pubmed]
  21. A DNA-binding-independent pathway of repression by the Drosophila Runt protein. Vander Zwan, C.J., Wheeler, J.C., Li, L.H., Tracey, W.D., Gergen, J.P. Blood Cells Mol. Dis. (2003) [Pubmed]
  22. Repression of Drosophila photoreceptor cell fate through cooperative action of two transcriptional repressors Yan and Tramtrack. Lai, Z.C., Fetchko, M., Li, Y. Genetics (1997) [Pubmed]
  23. Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio. Pritchard, D.K., Schubiger, G. Genes Dev. (1996) [Pubmed]
  24. Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. Guo, M., Jan, L.Y., Jan, Y.N. Neuron (1996) [Pubmed]
  25. Tramtrack69 is required for the early repression of tailless expression. Chen, Y.J., Chiang, C.S., Weng, L.C., Lengyel, J.A., Liaw, G.J. Mech. Dev. (2002) [Pubmed]
  26. Repression of Drosophila pair-rule segmentation genes by ectopic expression of tramtrack. Brown, J.L., Wu, C. Development (1993) [Pubmed]
 
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