Please use this identifier to cite or link to this item: https://doi.org/10.1161/ATVBAHA.113.301428
Title: Two isoforms of sister-of-mammalian grainyhead have opposing functions in endothelial cells and in vivo
Authors: Haendeler, J.
Mlynek, A.
Buchner, N.
Lukosz, M.
Graf, M.
Guettler, C.
Jakob, S.
Farrokh, S.
Kunze, K.
Goy, C.
Guardiola-Serrano, F.
Schaal, H.
Cortese-Krott, M.
Deenen, R.
Kohrer, K.
Winkler, C. 
Altschmied, J.
Keywords: Apoptosis
Cell movement
Human umbilical vein endothelial cells
Nitric oxide
Sister-of-mammalian grainyhead protein human
Transcription factors
Zebrafish
Issue Date: Jul-2013
Citation: Haendeler, J., Mlynek, A., Buchner, N., Lukosz, M., Graf, M., Guettler, C., Jakob, S., Farrokh, S., Kunze, K., Goy, C., Guardiola-Serrano, F., Schaal, H., Cortese-Krott, M., Deenen, R., Kohrer, K., Winkler, C., Altschmied, J. (2013-07). Two isoforms of sister-of-mammalian grainyhead have opposing functions in endothelial cells and in vivo. Arteriosclerosis, Thrombosis, and Vascular Biology 33 (7) : 1639-1646. ScholarBank@NUS Repository. https://doi.org/10.1161/ATVBAHA.113.301428
Abstract: Objective-Sister-of-Mammalian Grainyhead (SOM) is a member of the Grainyhead family of transcription factors. In humans, 3 isoforms are derived from differential first exon usage and alternative splicing and differ only in their N terminal domain. SOM2, the only variant also present in mouse, induces endothelial cell migration and protects against apoptosis. The functions of the human specific isoforms SOM1 and SOM3 have not yet been investigated. Therefore we wanted to elucidate their functions in endothelial cells. Approach and Results-Overexpression of SOM1 in primary human endothelial cells induced migration, phosphorylation of Akt1 and endothelial nitric oxide synthase, and protected against apoptosis, whereas SOM3 had opposite effects; isoform-specific knockdowns confirmed the disparate effects on apoptosis. After reporter assays demonstrated that both are active transcription factors, microarray analyses revealed that they induce different target genes, which could explain the different cellular effects. Overexpression of SOM3 in zebrafish embryos resulted in increased lethality and severe deformations, whereas SOM1 had no deleterious effect. Conclusions-Our data demonstrate that the splice variant-derived isoforms SOM1 and SOM3 induce opposing effects in primary human endothelial cells and in a whole animal model, most likely through the induction of different target genes. © 2013 American Heart Association, Inc.
Source Title: Arteriosclerosis, Thrombosis, and Vascular Biology
URI: http://scholarbank.nus.edu.sg/handle/10635/102082
ISSN: 10795642
DOI: 10.1161/ATVBAHA.113.301428
Appears in Collections:Staff Publications

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