Disease relevance of Epb4.9

• Loss of heterozygosity on 8p in prostate cancer implicates a role for dematin in tumor progression [1].
• One allele of dematin was also deleted in the established prostate adenocarcinoma cell line PC-3, which displays a classic oncogenic phenotype [1].

High impact information on Epb4.9

• In vitro membrane stability measurements indicated significantly greater membrane fragmentation of the dematin headpiece null erythrocytes [2].
• By using homologous recombination in mouse embryonic stem cells, the headpiece domain of dematin was deleted to evaluate its function in vivo [2].
• Dematin is localized to the spectrin-actin junctions, and its actin-bundling activity is regulated by phosphorylation of cAMP-dependent protein kinase [2].
• The carboxyl terminus of dematin is homologous to the "headpiece" domain of villin, an actin-bundling protein of the microvillus cytoskeleton [2].
• Together, these results reveal an essential role of dematin and adducin in the maintenance of erythrocyte shape and membrane stability, and they suggest that the dematin-membrane interaction could link the junctional complex to the plasma membrane in erythroid cells [3].

Biological context of Epb4.9

• The gene encoding the erythrocyte membrane skeleton protein dematin (Epb4.9) maps to mouse chromosome 14 [4].
• Overexpression of wild-type dematin in PC-3 cells resulted in the restoration of a more polarized, epithelial-like phenotype [1].
• These results suggest a biological function of dematin in the regulation of cell shape, with implications in the pathobiology of prostate tumorigenesis [1].
• Radiation hybrid mapping now places dematin between D8S258 and D8S137, two microsatellite markers frequently deleted in prostate cancer [1].

Anatomical context of Epb4.9

• Together, these results provide evidence for the physiological significance of dematin and demonstrate a role for the headpiece domain in the maintenance of structural integrity and mechanical properties of erythrocytes in vivo [2].
• Transcripts of dematin are widely distributed including human brain, heart, lung, skeletal muscle, and kidney [5].
• Dematin is a cytoskeletal protein that bundles actin filaments in a phosphorylation-dependent manner [1].
• Conversely, the heterologous expression of dominant negative mutants of dematin perturbed normal cell morphology of NIH 3T3 fibroblasts [1].

Associations of Epb4.9 with chemical compounds

• Here, we show that dematin interacts with the guanine nucleotide exchange factor Ras-GRF2 by yeast two-hybrid assay, and this interaction is further confirmed by blot overlay, surface plasmon resonance, co-transfection, and co-immunoprecipitation assays [5].

Other interactions of Epb4.9

• Here we report generation and characterization of double knock-out mice lacking beta-adducin and the headpiece domain of dematin [3].
• Like dematin, RET52 is also a substrate for cAMP-dependent protein kinase [6].

Analytical, diagnostic and therapeutic context of Epb4.9

• To investigate the physiological function of dematin, we employed the yeast two-hybrid assay to identify dematin-interacting proteins in the adult human brain [5].
• Using laser-capture microdissection technique and fluorescence in situ hybridization (FISH), we demonstrate loss of heterozygosity (LOH) of the dematin gene in a majority of chromosomal region 8p21-linked prostate tumors [1].

References