Disease relevance of ENAH

• PURPOSE: hMena (ENAH), a cytoskeleton regulatory protein involved in the regulation of cell motility and adhesion, is overexpressed in breast cancer [1].
• In these cells, Shigella form normal-appearing actin tails and move at rates that are comparable to the rates of bacterial movement in Ena/VASP-deficient cells complemented with the Ena/VASP family member Mena [2].
• The Mena EVH1 domain, a protein-interaction module involved in actin-based cell motility, recognizes proline-rich ligand motifs, which are also present in the sequence of the surface protein ActA of Listeria monocytogenes [3].
• To examine the influence of age on the autonomic and electrophysiological correlates of sudden death after myocardial infarction, 223 patients aged less than 60 and 195 patients aged greater than or equal to 60 were followed up for a mena of 790 days [4].

High impact information on ENAH

• Coimmunoprecipitations demonstrate that in vivo Tes is complexed with actin, Mena, and vasodilator-stimulated phosphoprotein (VASP) [5].
• APP and FE65 colocalize with actin and Mena, an Abl-associated signaling protein thought to regulate actin dynamics, in lamellipodia [6].
• hMena (ENAH), an actin regulatory protein involved in the control of cell motility and adhesion, is modulated during human breast carcinogenesis [7].
• Molecular cloning of hMena (ENAH) and its splice variant hMena+11a: epidermal growth factor increases their expression and stimulates hMena+11a phosphorylation in breast cancer cell lines [7].
• It also binds and activates IRSp53, which recruits the Ena/WASP family protein Mena to the filopodial tip and protects elongating actin filaments from capping [8].

Biological context of ENAH

• By transfection assays we showed that zyxin interaction with Mena/VASP in vivo enhances the production of actin-rich structures at the apical surface of cells [9].
• Structure-based synthetic mimicry of discontinuous protein binding sites: inhibitors of the interaction of Mena EVH1 domain with proline-rich ligands [3].
• Based on the crystal structure of Mena EVH1 in complex with a polyproline peptide ligand, we have generated a range of assembled peptides presenting the Mena EVH1 fragments that make up its discontinuous binding site for proline-rich ligands [3].

Anatomical context of ENAH

• The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors [1].
• Mena and IRSp53 act synergistically to promote filopodia formation [10].
• The reduction in Mena/VASP binding was confirmed by peptide tests, immunoprecipitation, and ectopic expression of zyxin variants at the surface of mitochondria [9].
• Using fibroblasts lacking Mena and VASP, we show that these proteins are not required to recruit Tes to focal adhesions [5].
• Moreover, when EphB4 and ephrin-B2 were expressed in neighbouring Swiss 3T3 fibroblasts, VASP and Mena co-accumulated with activated Eph receptors at protrusions formed by EphB4-expressing cells [11].

Associations of ENAH with chemical compounds

• Recent studies have revealed that profilin interacts with VASP, Mena, Bnilp, Bnrlp, and mDia, all of which have the proline-rich domain [12].
• Although mena plasma cortisol decresed, individual changes in cortisol did not correlate with changes in plasma aldosterone [13].
• A comparison of radiation-sensitizing ability and cell uptake for NDPP and Ro-07-0582 [14].
• During the course of intravenous infusion therapy, a progressive increase in mena osmolality was observed, accompanied by a rise in blood glucose, sodium and urea levels [15].
• When normal monocytes were cultured together with LPS and IFN gamma, mena IL 1 alpha production was 297 +/- 56 U/ml [16].

Physical interactions of ENAH

• Our data suggest that Mena binding to F-actin allows for gephyrin recruitment to the leading edge of uncapped actin filaments [17].
• Myosin X transports Mena/VASP to the tip of filopodia [18].

Other interactions of ENAH

• Using affinity chromatography, we have identified Mena, an Ena/VASP family member, as interacting with the SH3 domain of IRSp53 [10].
• These results indicate that N-WASP, WAVE and Mena have different roles in the regulation of the cortical actin cytoskeleton in the protruding lamellipodium [19].
• In this study, Mena and Hsp70 were detected as interaction partners to profilin:actin [20].

Analytical, diagnostic and therapeutic context of ENAH

• By immunofluorescence and immunoelectron microscopy, both WAVE and Mena were observed to localize at the lamellipodium edge [19].
• Immunocytochemistry revealed that endogenous M10 co-localized with Mena/VASP at the tip of filopodia [18].
• METHODS: In a cross-sectional study we compiled data on all patients admitted to 1487 beds in four hospitals in Mena (793 beds) and three hospitals in Arafat (694 beds) from the seventh to the thirteenth day of the Hajj season of the Islamic year 1423, corresponding to 8 to 14 February 2003 [21].

References