The subgroup C of the adenoviruses (Ad) and the group B coxsackieviruses (CVB) are structurally unrelated viruses that are known to compete for an unidentified cell surface receptor. We now describe the isolation of cDNAs from human and mouse that encode the human CVB and Ad2 and 5 receptor (HCAR) and the mouse CVB Ad2 and 5 receptor (MCAR). Both are 46-kDa glycoproteins whose primary amino acid sequences are highly homologous. Structurally, HCAR and MCAR appear to be transmembrane proteins that contain two extracellular immunoglobulin-like domains and therefore belong to this superfamily. Transfection of either of these cDNA molecules into receptor-negative NIH 3T3 cells conferred susceptibility to CVB infection and permitted the expression of ␤-galactosidase from a recombinant Ad5 vector. In addition, HCAR and MCAR mRNAs could be detected on Northern blots of oligo(dT)-selected RNA from receptor-positive HeLa cells and TCMK-1 as well as several tissues of human and mouse origin that are known to be targets for Ad and CVB infections. Finally, Western blots using antibodies that inhibit virus binding to either the human or mouse CVB receptors detected 46-kDa proteins in HCARand MCAR-transfected cells, respectively. Taken together, these results confirm that the isolated cDNAs encode the receptors for the subgroup C Ad and CVB.The ability of animal viruses to infect host cells is dependent on the presence of an appropriate cellular receptor. In general, viruses of different families do not compete for binding to a common receptor. However, adenovirus (Ad) serotypes 2 (Ad2) and 5 (Ad5) and the parental group B coxsackieviruses (CVB) are human pathogens that obviously share a common receptor although they belong to divergent virus families (1). The Ad are DNA viruses that contain fiber proteins protruding from the 5-fold vertices of an icosahedral capsid. It is the terminal portion of the fiber known as the ''knob'' that is responsible for receptor binding (2). In contrast, the CVB are RNA viruses that lack fiber structures and are presumed to attach to cells through insertion of the receptor into a ''canyon'' on the surface of the virus (3). Interestingly, although these viruses use a common receptor they do not exhibit a similar host range (4). The CVB are known to infect a variety of organs, including the brain, intestines, heart, pancreas, and lungs, whereas the Ad primarily infect the intestines and lungs (4, 5). Therefore, these differences must be due to restrictions within the Ad life cycle subsequent to receptor attachment. We demonstrate here that transfection of either HCAR or MCAR cDNA into receptor-negative NIH 3T3 cells is sufficient to confer susceptibility to subgroup C Ad and CVB infection. MATERIALS AND METHODScDNA Library Screening. Five micrograms of twice oligo-(dT)-selected TCMK-1 RNA was used to construct a cDNA library in the ZAP Express vector using the ZAP Express cDNA synthesis kit (Stratagene). A library of 4 ϫ 10 5 primary clones was amplified once in the XL1-Blue MRFЈ strain of...

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Epithelial-mesenchymal transitions (EMT) are essential for organogenesis and triggered in carcinoma progression into an invasive state1. Transforming growth factor-β (TGF-β) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT2-5, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT6, 7. The SNAIL1-SMAD3/4 complex was targeted to the gene promoters of CAR, a tight junction protein, and E-cadherin during TGF-β-driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells. Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited the repression of CAR and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma and at the invasive fronts of human breast cancer. We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a novel mechanism of gene repression during EMT.