Disease relevance of ETV5

• Overexpression in these malignancies suggests ETV5 as a new candidate for a pathogenic factor in B-cell lymphomas [1].
• Listeria monocytogenes exploits ERM protein functions to efficiently spread from cell to cell [2].
• Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin [3].
• This study demonstrates for the first time that ERM gene expression is an independent adverse prognostic factor for overall survival in breast cancer patients [4].
• Altered expression of the ERM proteins in lung adenocarcinoma [5].
• The specific localization of ERM/ETV5 and MMP-2 at the invasive front of myometrial infiltrating human endometrial carcinomas further reinforced the hypothesis of a role for ERM/ETV5 in the early steps of endometrial dissemination [6].

Psychiatry related information on ETV5

• Using the ERM apparatus (Schuhfried Instruments, Austria), which measures choice reaction time to a task with high cognitive content, it was found that both decision and reaction time increased as a function of rising BAC, and that movement time was not affected [7].

High impact information on ETV5

• Understanding ERM proteins - the awesome power of genetics finally brought to bear [8].
• ERM proteins and NF2 tumor suppressor: the Yin and Yang of cortical actin organization and cell growth signaling [9].
• The ERM (ezrin, radixin and moesin) family of proteins are linkers that tether actin microfilaments to the plasma membrane [9].
• In ERM proteins and merlin, interdomain binding promotes auto-inhibition and homo-oligomerization or hetero-oligomerization [9].
• Recent studies have revealed that ERM proteins transduce growth signals, and have shed new light on how merlin links cell growth to the cytoskeleton [9].

Biological context of ETV5

• Assignment of the ERM gene (ETV5) coding for the ets-related protein to human chromosome band 3q28 by in situ hybridization [10].
• Interfering with either of these interactions or with ERM proteins phosphorylation not only reduces the number of protrusions but also alters their morphology, resulting in the formation of short and collapsed protrusions [2].
• These results demonstrate that ERM is subject to SUMO modification and that this post-translational modification causes inhibition of transcription-enhancing activity [11].
• In in vivo transient-expression assays, ERM induced transcription more efficiently from a synthetic element containing both an ets-binding site (EBS) and a cyclic AMP response element (CRE) than from one containing an EBS alone [12].
• Prognostic value of ERM gene expression in human primary breast cancers [4].

Anatomical context of ETV5

• ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1 [13].
• Moesin, the major ERM protein of lymphocytes and platelets, differs from ezrin in its insensitivity to calpain [14].
• Because Ca signaling pathways involving calpain cleavages are important in blood cells, we examined ERM protein sensitivity to this protease [14].
• The ability of Listeria to induce protrusions and effectively spread between adjacent cells depends on the interaction of ERM proteins with both a membrane component such as CD44 and actin filaments [2].
• These results biochemically connect merlin to the cortical cytoskeleton and indicate differential regulation of merlin from ERM proteins [3].

Associations of ETV5 with chemical compounds

• Using fluorescence lifetime imaging microscopy, PKCalpha is shown to form a molecular complex with ezrin, and the PKC-co-precipitated endogenous ERM is hyperphosphorylated at the C-terminal threonine residue, i.e. activated [15].
• Upon phorbol 12,13-dibutyrate stimulation, green fluorescent protein-PKCalpha and beta1 integrins co-sediment with ERM proteins in low-density sucrose gradient fractions that are enriched in transferrin receptors [15].
• Moreover, in vitro translation of 83 AA of the ERM ETS domain led to the production of a truncated protein which also binds to DNA [16].
• In multivariate analyses, ERM preserved its prognostic value (P = 0.004; risk ratio, 3.779) together with histoprognostic grading, tumor size, estradiol receptors, and progesterone receptors [4].
• The NH(2)- and COOH-terminal association domains of ERM proteins, known respectively as N-ERMAD and C-ERMAD, participate in interactions with membrane proteins and F-actin, and intramolecular and intermolecular interactions within and among ERM proteins [17].

Physical interactions of ETV5

• Indeed, CIC-DUX4 directly binds the ERM promoter by recognizing a novel target sequence and significantly up-regulates its expression [18].
• The C-terminal actin-binding site in the ERM proteins and the actin-binding helix in the villin headpiece have a common amino acid motif [19].
• ERM proteins are conformationally regulated - binding sites for EBP50 and F actin are masked in the dormant molecules and activation leads to exposure of these sites [20].
• ERM protein binding and actin anchoring by NHE1 are necessary to retain the localization of NHE1 in specialized plasma membrane domains and to promote cytoskeleton-dependent processes, including actin filament bundling and cell-substrate adhesions [21].
• Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition [22].

Enzymatic interactions of ETV5

• This study tested the hypothesis that ERM proteins are phosphorylated on this critical threonine residue through TNF-alpha-induced activation of PKC and p38 and modulate permeability increases in pulmonary microvascular ECs [23].

Regulatory relationships of ETV5

• TNF-alpha-induced ERM phosphorylation was accompanied by cytoskeletal changes, paracellular gap formation, and increased permeability to fluxes of dextran and albumin [23].

Other interactions of ETV5

• Moesin is the quantitatively dominant ERM protein in these cells and the only one in platelets [14].
• Notably, only 3 genes (ETV5, DUSP6, and KIAA0735) are uniquely induced in mutant ras-containing cells [24].
• The results suggest that ERM proteins are possible novel auto-immune target antigens for RA [25].
• In conclusion, NF2 protein possesses functional properties of an ERM family member [26].
• Using the chi2 test, a positive relationship was found between the expression of ERM and EGFR (chi2 = 7.795, P = 0.007) [4].

Analytical, diagnostic and therapeutic context of ETV5

• Gel shift analysis indicates that the full-length ERM protein is able to bind specifically to an oligonucleotide containing the consensus nucleotide core sequence GGAA recognized by the Ets proteins [16].
• Gene expression levels of ERM/ETV5 were quantified by real-time quantitative PCR (RT-Q-PCR) using a large panel of samples ranging from non-invasive IA to metastatic IIIA stages, and protein expression was characterized by tissue array immunohistochemistry (TMA) [27].
• Immunocytochemistry and in vitro studies have suggested that the ERM (ezrin-radixin-moesin) protein, radixin, may have a role in nerve growth cone motility [28].
• To examine the biological significance of the exon-missing mutations in the ERM homology domain, we expressed the wild-type (wt-NF2) and the various mutant NF2s (mu-NF2s) in a fibroblast cell line by using both liposome-mediated transfection and nuclear microinjection of the expression plasmids [29].
• Quantitative immunoblotting revealed that the molar ratio of merlin/ERM in cultured epithelial or non-epithelial cells was approximately 0.14 or approximately 0.05, respectively [30].

References