Disease relevance of APPBP2

• Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets [1].
• Association of the herpes simplex virus type 1 Us11 gene product with the cellular kinesin light-chain-related protein PAT1 results in the redistribution of both polypeptides [2].
• 17q23 amplifications in breast cancer involve the PAT1, RAD51C, PS6K, and SIGma1B genes [3].

High impact information on APPBP2

• Treatment of cells with lactacystin prevents PAT1 degradation and retains its nuclear localization [4].
• Cotransfection of PAT1 with a reporter protein shows that PAT1 is functionally linked with intracellular transport of APP [5].
• PAT1 shows homology to kinesin light chain, which is a component of the plus-end directed microtubule-based motor involved in transporting membrane proteins to the basolateral surface [5].
• PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein [5].
• We propose that PAT1 is involved in the translocation of APP along microtubules toward the cell surface [5].

Biological context of APPBP2

• CONCLUSIONS: Information gained from our relatively large panel of OCCA tumors suggested that 17q21-q24 gain and consequent overexpression of two potential targets, PPM1D and APPBP2, are associated with malignant phenotypes of this tumor and may be useful predictors for prognosis [1].
• The carboxyl-terminal dsRNA-binding domain of Us11, which also contains the nucleolar retention and nuclear export signals, binds PAT1, whereas 149 residues derived from the KLC homology region of PAT1 are important for binding to Us11 [2].
• Substrate specificity of the amino acid transporter PAT1 [6].
• Influence of a proton gradient on the transport kinetics of the H+/amino acid cotransporter PAT1 in Caco-2 cells [7].
• The nucleotide and deduced amino acid sequences of the RPB2 gene in Pat1 were closely related to that in PN-w [8].

Anatomical context of APPBP2

• PAT1, a cytoplasmic protein, associates with membranes, cofractionates with APP-containing vesicles, and binds microtubules in a nucleotide-sensitive manner [5].
• The proteins TIP47, S3-12, and OXPAT/MLDP/PAT-1 move from the cytosol to coat nascent lipid droplets during rapid fat storage [9].
• The role of Slc26a6 (PAT1) on apical Cl(-)/HCO(3)(-) exchange and bicarbonate secretion in pancreatic duct cells was investigated using Slc26a6 null and wild-type (WT) mice [10].
• Because human intestine expresses hPAT1 at the brush border membrane, the transporter may serve as a new oral drug delivery route [7].

Associations of APPBP2 with chemical compounds

• Here we report identification of a protein, termed PAT1 (protein interacting with APP tail 1), that interacts with the APP-BaSS but binds poorly when the critical tyrosine is mutated and does not bind the tyrosine-based endocytic signal of APP [5].
• We systematically analyzed the structural requirements for PAT1 substrates by testing 87 amino acids, proline homologs, indoles, and derivatives [6].
• PAT1 interacts strongly with heterocyclic aromatic acids containing an indole scaffold [6].
• The recently cloned proton-coupled amino acid transporter 1 (PAT1) not only accepts several amino acids as substrates but also pharmaceutically relevant L-proline or GABA derivatives such as cis-4-hydroxy-L-proline, L-azetidine-2-carboxylic acid (LACA), 3-amino-1-propanesulfonic acid, nipecotic acid, and the antituberculotic agent D-cycloserine [7].

Other interactions of APPBP2

• S6K, PAT1, and TBX2 were coamplified in about 10% of tumors, whereas RADS1C amplification was seen in only 3% of tumors [11].

Analytical, diagnostic and therapeutic context of APPBP2

• Among 15 candidate genes within the 17q21-q24 region, we found significantly elevated expression of PPM1D and APPBP2, and their heightened expression correlated negatively with disease-free survival (P = 0.0090, log-rank test adjusted for multiple comparisons) [1].

References