Disease relevance of ttk

• Mayven contains a BTB (broad complex, tramtrack, bric-a-brac)/POZ (poxvirus, zinc finger) domain-like structure in the predicted N terminus and "kelch repeats" in the predicted C-terminal domain [1].

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

• On the basis of these results, we propose that bft acts downstream of cut and tramtrack to implement correct bristle morphogenesis [17].

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

• Whole mount in situ hybridization analysis revealed different patterns of embryonic expression of the two ttk mRNA isoforms [6].
• Consistent with this hypothesis, we have detected by immunohistochemistry the presence of ttk protein in preblastoderm embryos [26].

References