Disease relevance of DAB1

• Treatment of pancreatic cancer cells with histone deacetylase inhibitors, valproic acid and suberoylanilide hydroxamic acid, restored the expression of RELN and DAB1 and markedly inhibited their migration [1].
• No mutations of the dab1 and p35 genes in gangliogliomas were observed [2].
• Povidone-iodine was 100 percent effective at a dilution of 12.5% against Staphylococcus epidermidis and 25% against Staphylococcus aureus but relatively ineffective against Escherichia coli and Pseudomonas, DAB-1 was found to be ineffective against S. epidermidis but effective against S. aureus, Propionibacterium acnes, E. coli, and Pseudomonas [3].
• To investigate the in vivo efficacy of gene therapy with the gelsolin gene, we inoculated nude mice with human urinary bladder cancer cells (UMUC-2 or DAB-1) and tested the effects of adding either retroviral DNA constructs containing gelsolin cDNA or retrovirus producer cells that produce the same retroviral constructs at high levels [4].

Psychiatry related information on DAB1

• In humans, Reelin mutations are associated with brain malformations and mental retardation; mutations in DAB1 have not been identified [5].

High impact information on DAB1

• Increased cell motility was also induced by knockdown of downstream components of the RELN pathway, including ApoER2, VLDLR, and DAB1 [1].
• Using a genetic complementation approach we have identified disabled-2 (Dab2), a structural homolog of the Dab1 adaptor molecule, as a critical link between the transforming growth factor beta (TGFbeta) receptors and the Smad family of proteins [6].
• METHODS: Reelin, GAD(65), GAD(67), DAB1, and neuron-specific-enolase messenger RNAs (mRNAs) and respective proteins were measured with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analyses [7].
• DAB1 and Reelin Effects on Amyloid Precursor Protein and ApoE Receptor 2 Trafficking and Processing [8].
• These effects depended on the NPXY domains of APP and apoEr2 and on the phosphotyrosine binding domain of Dab1 but did not depend on phosphorylation of Dab1 [8].

Biological context of DAB1

• We further determined the cellular expression of the proteins RELN and DAB1 in 50 human brains ranging in age from 10 gestational weeks (GW) to 62 years using immunochemistry [9].
• Loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler-like phenotype [10].
• Alternative polyadenylation and splicing events generate DAB1 isoforms [5].
• Yet, the third exons of DAB1 and DAB2 were identical in all available sequences and differed at 10 positions from the exon 3 sequences of B-LBI/B-LBII [11].
• Given the divergence in the 3'UT region, the finding of the same exon 2 sequence at both the DAB1 and the DAB2 loci in one of the pheasant haplotypes also suggests that interlocus genetic exchange does occur [11].

Anatomical context of DAB1

• Radially orientated apical dendrites of Dab1-expressing neurons indicated a predominant pyramidal phenotype [12].
• Pyramidal cells in hippocampus and entorhinal cortex displayed a more protracted time of Dab1 expression compared to neocortex [12].
• The medial and dorsal cortical plate and Purkinje cells were reelin-negative but expressed disabled-1 (Dab1) mRNA [13].
• Gene expression of dab1 and p35 was determined by real-time RT-PCR (reverse transcriptase polymerase chain reaction) in gangliogliomas (n = 14) vs. non-neoplastic central nervous system tissue (n = 20) [2].
• Formation of the mammalian six-layered neocortex depends on a signaling pathway that involves Reelin, the very low-density lipoprotein receptor, the apolipoprotein E receptor-2 (ApoER2), and the adaptor protein Disabled-1 (Dab1) [14].

Associations of DAB1 with chemical compounds

• In the Reln(rl/rl) cortex, CRMP1 and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower level [10].
• The total syntheses of DAB1 (1) and (-)-lentiginosine (2) were concisely accomplished from D-lyxose via regioselective and diastereoselective NHCbz introduction using CSI, chemoselective removal of the Cbz protection, and ring-closing metathesis as key steps [15].
• The tetra-BOC derivatives 1b and 1c were used to prepare several Polymyxin B derivatives 6-27 at the DAB1 and DAB9-gamma-amine [16].
• Full-length Dab1 or its phosphotyrosine binding domain alone increased surface levels of APP, as determined by surface protein biotinylation and live cell staining [8].
• In phase II, povidone-iodine was serially diluted in DAB-1 rather than saline [3].
• We show that degradation of Dab1 depends on Dab1 phosphorylation at specific tyrosine residues and on the E3 ubiquitin ligase component Cullin 5 (Cul5) [17].

Physical interactions of DAB1

• This finding explains how the Dab1 PTB domain can simultaneously bind PI and the ApoER2 tail [14].

Other interactions of DAB1

• In the same samples of temporal cortex, we found a decrease in RELN protein of approximately 50% but no changes in DAB1 protein expression [18].
• The phylogenetic relationships and patterns of nucleotide substitution were compared for introns and exons of class II major histocompatibility complex (MHC) genes in three datasets: human DRB1, human DQA1, and cyprinid fish DAB1 [19].
• Together, these data suggest that Dab1 alters trafficking and processing of APP and apoEr2, and this effect is influenced by extracellular ligands [8].
• This review focuses on two related PTB domain containing adaptor proteins that mediate these divergent lipoprotein receptor responses, ARH (autosomal recessive hypercholesterolemia protein) and Dab1 (disabled-1), and discusses the structural and molecular basis of this different behaviour [20].
• A ligand for apoEr2, the extracellular matrix protein Reelin, significantly increased the interaction of apoEr2 with Dab1 [8].

Analytical, diagnostic and therapeutic context of DAB1

• Third, we present preliminary studies by in situ hybridization that demonstrate regulated expression of Reelin receptors and Dab1 by radial precursors in the ventricular zone [21].
• The purpose of this study was to compare the in vitro efficacy of serial dilutions of povidone-iodine and two double antibiotic solutions DAB-1 (gentamicin/polymyxin B) and DAB-2 (gentamicin/cefazolin), against organisms most commonly found around breast implants [3].

References