Disease relevance of Antp

• The homeodomain encoded by the Antennapedia (Antp) gene of Drosophila was overproduced in a T7 expression vector in Escherichia coli [1].
• Instead, it mimics Antp in directing T2 denticle pattern, and it can rescue the cuticular loss-of-function phenotype of Antp mutants [2].
• Protein transduction domains (PTDs), such as the third helix of the Drosophila Antennapedia homeobox gene (Antp) and the HIV TAT PTD, possess a characteristic positive charge on the basis of their enrichment for arginine and lysine residues [3].
• Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency [4].
• Fusion of W45 to membrane translocation signals from HIV-1 tat protein (YGRKKRRQRRRPP-LRK(5)H, DT-2) or Drosophila Antennapedia homeo-domain (RQIKIWFQNRRMKWKK-LRK(5)H, DT-3) proved to be an efficient method for intracellular delivery of these highly charged peptides [5].

Psychiatry related information on Antp

• We suggest that Ns-protein deficiency, reduced cAMP levels, or both, are involved in the mental deficiency in these patients and probably in mental function in humans [4].

High impact information on Antp

• In head and thorax the Ubx product overrides Sex combs reduced, Antennapedia, and probably other homeotic genes and dictates its own developmental program [6].
• Here we describe a cotransfection assay in cultured D. melanogaster cells that is used to demonstrate that Ubx proteins (UBX) can repress an Antp promoter fusion and activate a Ubx promoter fusion, activities predicted from genetic studies [7].
• A TAA-rich DNA sequence to which the Antp protein binds in vitro is sufficient to confer regulation on a heterologous promoter [8].
• Sequences downstream of the Antp P1 and Ultrabithorax transcription start sites mediate the observed activation [8].
• Using a cotransfection assay, we have shown that homeodomain proteins encoded by the homeotic gene Antennapedia (Antp) and the segmentation gene fushi tarazu, as well as a hybrid homeodomain protein, are activators of transcription from specific promoters in cultured Drosophila cells [8].

Biological context of Antp

• The protein binds tightly to sequences near its own promoter and near the P1 promoter of Antenna-pedia (Antp), a homeotic gene Ubx is known to repress from genetic studies [9].
• The binding sites occur in clusters downstream of the transcription start sites, and far upstream at Antp P1 [9].
• The time course of the interaction and reporter gene fusion experiments suggests (but does not prove) a direct interaction between Antp and cis-regulatory elements of salm [10].
• To obtain a more comprehensive view of how individual enhancers selectively interact with appropriate target genes, we used bioinformatic methods to identify new cis-regulatory DNAs in the approximately 50-kb Scr-Antp interval [11].
• We show that the DNA elements driving tissue-specific transcriptional activation by Antp and Ubx are separable [12].

Anatomical context of Antp

• Antp is expressed in the nuclei of cells of the thoracic embryonic epidermis and several segments of the ventral and peripheral nervous systems [13].
• Antp activates tsh in anterior midgut mesoderm [14].
• We have sequenced the region containing the homeotic selector genes required for proper development of the head and anterior thorax, which is the counterpart of the ANTC in Drosophila [15].
• Three observations rule out a cell autonomous role for ANTP in tarsus determination [16].
• This hypothesis was tested by inserting the complementary DNA encoding the normal Antp protein into a heat-shock expression vector and subsequent germ-line transformation [17].

Associations of Antp with chemical compounds

• These experiments indicate that the ninth amino acid of the recognition helix of the homeodomain, which is glutamine in all four of these Antp-type homeodomain proteins, is not sufficient to determine their DNA binding specificities [18].
• Despite the hydrophobic nature of this tetrapeptide motif, the N-terminal arm consisting of residues -14 to 6 is flexibly disordered, and the well-defined part of the HD structure with residues 7-59 is indistinguishable from that of the shorter Antp HD polypeptide (where positions 0, 1, and 67 are methionine, arginine, and glycine, respectively) [19].
• This hypoactive form of ANTP, but not the alanine-substituted form, is also reduced in its ability to bind to DNA cooperatively with the homeodomain protein Extradenticle [20].
• The mobility shift assay was used to study the competition of the minor groove binder distamycin A with either an Antennapedia homeodomain (Antp HD) peptide or derivatives of a fushi tarazu homeodomain (ftz HD) peptide for their AT-rich DNA binding site [21].
• Exposure of Ns and ssa40a larvae to half-lethal concentrations of 5-bromodeoxyuridine (BUdR) and flourouracil (FU) together or separately during the presumptive time of gene action suppresses the expressivity and penetrance of the mutants [22].

Physical interactions of Antp

• The three Hox genes of the Bithorax Complex as well as Antennapedia (Antp) have been shown to be expressed in the posterior cardiac tube, while no Hox gene is expressed in the anterior aorta [23].
• Restriction fragments containing ftz homeodomain binding sites were identified within a 90 kb stretch of DNA extending the Antp P1 and P2 promoters [24].
• We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes [25].

Regulatory relationships of Antp

• Taken together, these data indicate that hth is an antennal selector gene, and that Antp promotes leg development by repressing hth and consequently nuclear Exd [26].
• Therefore, we conclude that Antp negatively regulates salm [10].
• The good correlation between the in vitro DNA binding preferences of these four Antp-type homeodomain proteins and their ability to specifically regulate a Dfd enhancer element in the embryo, suggests that the modest binding differences that distinguish them make an important contribution to their unique regulatory specificities [18].
• In the epidermis, Antp has been shown to negatively regulate Scr, but it positively regulates Scr in the visceral mesoderm [27].
• We have mapped the cis-acting control sequences of the homeotic Antennapedia (Antp) gene regulated by Pc [28].

Other interactions of Antp

• Here we assess the functional significance of some of these interactions by expressing the Antp, Ubx or both homoeotic genes under the control of the heat-shock promoter [29].
• Third, Antp is a repressor of hth [26].
• First, removing the function of exd or hth, which is required for the nuclear localization of Exd protein, transforms the antenna into leg; such transformations occur without activation of Antp [26].
• Here we show that mutations in several of the gap genes strongly alter the early patterns of Antp and Abd-B expression [30].
• DNA from each of these 3' exons also hybridized weakly to DNA from the fushi tarazu locus of the ANT-C [31].
• BIP2 is a TATA-binding protein associated factor (also known as dTAFII3) that links ANTP to the basal transcriptional machinery [32].

Analytical, diagnostic and therapeutic context of Antp

• By in situ hybridization of an Antp+ cDNA probe to tissue sections of these embryos, we have found that the neural cells of the transformed segments accumulate Antp+ transcripts to a level characteristic of the normal mesothorax [33].
• Antp is expressed in visceral mesoderm cells that overlie a part of the midgut where a constriction will form, and Antp null mutant embryos fail to form this constriction [27].
• A degenerate PCR screening for Hox/HOM homeoboxes in three species of triclad planarians has revealed 10 types of Antennapedia-like genes [34].
• Sequence determination of two of the clones containing the homeo-box regions reveals a 180-nucleotide(nt) domain sharing more than 80% homology at the nucleotide level and more than 90% homology at the amino acid level with the homeo-box from the Antp gene and from homeo-boxes of other metazoan species [35].
• The positions of these three helices correspond extremely well to those of the Drosophila Antennapedia (Antp) and engrailed (en) homeo domains, whose three-dimensional structures have recently been determined by NMR spectroscopy and X-ray crystallography, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[36]

References