Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exon trapping from a bacterial artificial chromosome (BAC 78138) mapping to the 19q13.3 glioma tumor suppressor candidate region yielded two exons that recognized a 3.6-kb transcript on Northern blot. Screening of a human fetal brain cDNA library with these exons identified three novel genes, designated EHD2, EHD3, and EHD4, which are homologous to the recently characterized human EHD1 (testilin/HPAST) and its mouse homolog Ehd1, as well as to homologs in Drosophila (Past1) and Caenorhabditis elegans. Alignment of the predicted peptide sequences revealed striking similarities, with multiple conserved regions that include a nucleotide-binding consensus site at the N-terminus, a bipartite nuclear localization signal, and an eps15 homology (EH) protein-binding domain with an EF-hand motif at the C-terminus. The genes are specifically expressed, with EHD2 highly expressed in heart, EHD3 in brain and heart, and EHD4 in heart and pancreas. EHD2 was confirmed to originate from BAC 78138 at 19q13.3; radiation hybrid mapping localized EHD3 and EHD4 to 2p21 and 15q11.1, respectively; EHD1 has been previously mapped to 11q13. The three EHD1 paralogs therefore represent novel members of a family of human EH domain-containing proteins that may play a role in endocytosis and signaling. Mutation analysis of the five coding exons of EHD2 in gliomas failed to detect any tumor-specific alterations, thus indicating that EHD2 is an unlikely candidate for the 19q tumor suppressor gene.
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PMID:EHD2, EHD3, and EHD4 encode novel members of a highly conserved family of EH domain-containing proteins. 1067 36

EHD3 [Eps15 homology (EH) domain-containing protein 3] is a protein that resides in tubular and vesicular membrane structures and participates in endocytic recycling, although all its functions are unknown. Since Ehd3 is most abundantly expressed in brain tissues, we examined its role in brain cancer progression. Using immunohistochemistry, we report loss of EHD3 expression in gliomas, including low-grade astrocytomas, suggesting that this is an early event in gliomagenesis. EHD3 expression is also very low in most of glioma cell lines tested. In two cell lines, a bisulfite sequencing method identifies promoter hypermethylation as a mechanism of Ehd3 silencing, and its expression was restored by the demethylating agent 5-Azacytidine. Doxycycline-inducible restoration of EHD3 expression to glioma cells decreases their growth and invasiveness and induces cell cycle arrest and apoptosis. Furthermore, shRNA-mediated Ehd3 silencing increases cell growth. Using a xenograft model, we demonstrate Ehd3 growth inhibitory functions in glioma cells in vivo. We suggest that Ehd3 functions as a tumor suppressor gene and loss of its expression is a very common event in gliomas. This is the first study to highlight the importance of a member of the C-terminal EHD proteins in cancer and to link their functions to the cell cycle and apoptosis.
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PMID:Ehd3, a regulator of vesicular trafficking, is silenced in gliomas and functions as a tumor suppressor by controlling cell cycle arrest and apoptosis. 2430 26