Drosophila homeodomain proteins

Homeoboxes code for homeodomains, sequences of 60 amino acids that function as the DNA-binding regions of transcription factors. Each homeo-box gene in Drosophila is expressed only in its own characteristic subset of embryonic cells, and almost every embryonic cell contains a unique combination of homeodomain proteins. 

Lai, Z., Fortini, M. E., and Rubin, G. M. (1991). The embryonic expression patterns if zfh-1 and zfh-2, two Drosophila genes encoding novel zinc-finger homeodomain proteins. Mech. Dev. 34 123-134. 

An interesting case of regulation at the translation level was discovered on the example of the homeodomain protein bicoid (bed), which is important in Drosophila differentiation (Dubnau and Struhl, 1996). The bicoid protein is a transcriptional activator that binds a cognate DNA element and stimulates the transcription of the neighboring genes. Apart from its specific DNA-binding capabUity, the bicoid protein binds to 3 -, non-translating sequences of the mRNA of another homeodomain protein (caudal protein) to inhibit its translation. 

Walter, J., Biggin, M.D. 1996. DNA binding specificity of two homeodomain proteins in vitro and in Drosophila embryos. Proc. Natl. Acad. Sci. USA 93, 2680-2685. 

Homeodomain Proteins Many eukaryotic transcription factors that function during development contain a conserved 60-residue DNA-binding motif that is similar to the helix-turn-helix motif of bacterial repressors. Called homeodomain proteins, these transcription factors were first identified in Drosophila mutants in which one body part was transformed into another during development (Chapter 15). The conserved homeodomain sequence has also been found in vertebrate transcription factors, including those that have similar master control functions in human development. 

Peptides Derived from Homeodomain Proteins Can Translocate across a Cell Membrane. Homeodomain proteins are transcription factors that are expressed during development and, in some tissues, throughout adult life. These factors, which act by binding to DNA within the nucleus, must translocate across membranes to function. Recent studies suggest that the ability of peptides derived from the third helix of Drosophila Antennapedia homeobox (Antp-HD) to cross membranes is conferred by domains rich in basic amino acids (Table 8.8). A number of other proteins—such as HIV-1 Tat protein [62], transportan [63], and basic amino acid-rich model proteins [64]—have domains that provide a similar enhanced permeation function. 

Rep and Cro are bacteriophage 434 proteins Lam Rep and Cro are bacteriophage proteins CAP, Irp Rep, and Lac Rep are catabolite activator protein, Trp repressor, and fac repressor oiE. coli, respectively. Antpis the homeodomain protein of the Antennapedia gene of the fruit fly Drosophila melanogaster. The numbers in each sequence indicate the location of the HTH within the amino acid sequences of the various polypeptides. 

Han K, Jeon MJ, Kim KA, Park J, Choi SY. Efficient intracellular delivery of GFP by homeodomains of Drosophila Fushi-tarazu and Engrailed proteins. Mol Cells 2000 10 728-32. 

Johnson, F.B., Parker, E., Krasnow, M.A. 1995. Extradenticle protein is a selective cofactor for the Drosophila homeotics Role of the homeodomain and YPWM amino acid motif in the interaction. Proc. Natl. Acad. Sci. USA 92, 739-743. 

Kuziora, M.A., McGinnis, W. 1991. Altering the regulatory targets of the Deformed protein in Drosophila embryos by substituting the Abdominal-B homeodomain. Mech. Dev. 33, 83-94. 

Cdx (caudal) family members encode homeodomain transcription factors. The name caudal derives from the essential function of the gene product in the development of the posterior Drosophila embryo, a role that appears generally conserved across species. In vertebrates, Cdx proteins perform essential functions in the trophoblast, intestinal development, posterior specification and vertebral patterning. While this review focuses largely on the function of murine Cdx homologues, a number of relevant findings have been established initially from other systems, and will be briefly discussed. 

---