Disease relevance of AP-2

• Deletion and site-directed mutagenesis analysis of the MMP-2 promoter demonstrates that the Sp1 site at -91 to -84 base pairs and the AP-2 site at -61 to -53 base pairs are critical for constitutive activity of this gene in invasive astroglioma cell lines [1].

High impact information on AP-2

• The deduced primary amino acid sequence of AP-2 does not contain a domain resembling any previously identified DNA binding motif [2].
• Transfection of cDNA clones into Drosophila cells indicates that the AP-2 gene product can also activate gene expression in vivo in a DNA template-dependent manner [2].
• Here, we report the isolation and characterization of a human cDNA clone containing the entire protein-coding region of AP-2 [2].
• Expression of the AP-2 clone in bacteria yields a protein that binds to DNA and activates transcription in vitro in a comparable manner to native human AP-2 [2].
• However, an interesting feature of the AP-2 protein is a clustered arrangement of proline and glutamine residues that have been found recently within the activation domains of other transcription factors [2].

Biological context of AP-2

• The AP-2 transcription factor is required for joint formation and cell survival in Drosophila leg development [3].
• These findings reveal multiple functions for dAP-2 during morphogenesis of feeding and locomotor appendages and their neural circuitry, and provide a new paradigm for understanding AP-2 family transcription factors [4].
• An in vitro translation product of DAP-2 cDNA binds specifically to AP-2 consensus binding sites [5].
• The predicted amino acid sequence exhibits 42-45% overall identity with the vertebrate AP-2 proteins [5].
• In vitro DNase I footprinting, electrophoretic mobility shift assays, and reporter gene assays identified functional AP-2 and Sp1 sites in this region [6].

Anatomical context of AP-2

• Overexpression of GFP-stonin 2 interferes with recruitment of AP-2 to the plasma membrane and impairs internalization of the transferrin, epidermal growth factor, and low density lipoprotein receptors [7].
• The adaptor protein (AP) complexes AP-1, AP-2, and AP-3 mediate coated vesicle formation and sorting of integral membrane proteins in the endocytic and late exocytic pathways in mammalian cells [8].
• DAP-2 is expressed in discrete regions of procephalic neuroectoderm, the brain, ventral nerve cord, and maxillary segment during Drosophila embryogenesis, and in the brain, optic lobes, ventral nerve cord, antenno-maxillary complex, and antennal and leg imaginal disks in third instar larvae [9].
• Both Stoned proteins colocalize precisely with endocytotic proteins including the AP2 complex and Dynamin in the "lattice network" characteristic of endocytotic domains in Drosophila presynaptic terminals [10].
• In parallel with recent biochemical studies, this genetic analysis strongly suggests that Stoned proteins regulate the AP2-Synaptotagmin I interaction during synaptic vesicle endocytosis [10].

Other interactions of AP-2

• The AP-2 family of transcription factors (AP-2alpha, AP-2beta and AP-2gamma) is temporally and spatially regulated in mammals and has also been implicated in oncogenesis [5].
• Sequences encoding the InR, DPE, AP-2, and Sp1 sites were 100% conserved between human and murine KCC1 genes [6].

Analytical, diagnostic and therapeutic context of AP-2

• Whole-mount in situ hybridizations demonstrated that DAP-2 is expressed initially at stage 9 of Drosophila embryonic development and that DAP-2 transcripts are detected in regions of the brain, eye-antennal disc, optical lobe, antenno-maxillary complex, and in a subset of cells of the ventral nerve cord [5].

References