ZFIN ID: ZDB-PUB-130611-35
Two Isoforms of Sister-of-Mammalian Grainyhead Have Opposing Functions in Endothelial Cells and In Vivo
Haendeler, J., Mlynek, A., Büchner, N., Lukosz, M., Graf, M., Güttler, C., Jakob, S., Farrokh, S., Kunze, K., Goy, C., Guardiola-Serrano, F., Schaal, H., Cortese-Krott, M., Deenen, R., Köhrer, K., Winkler, C., and Altschmied, J.
Date: 2013
Source: Arterioscler. Thromb. Vasc. Biol.   33(7): 1639-1646 (Journal)
Registered Authors: Graf, Martin, Winkler, Christoph
Keywords: apoptosis, cell movement, humans, human umbilical vein endothelial cells, nitric oxide, sister-of-mammalian grainyhead protein, zebrafish
MeSH Terms:
  • Animals
  • Apoptosis
  • Cell Movement
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Enzyme Activation
  • Gene Expression Profiling/methods
  • Gene Expression Regulation
  • Genes, Reporter
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells/metabolism*
  • Humans
  • MCF-7 Cells
  • Nitric Oxide/metabolism
  • Nitric Oxide Synthase Type III/metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Protein Isoforms
  • Proto-Oncogene Proteins c-akt/metabolism
  • RNA Interference
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Transcription, Genetic
  • Transfection
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed: 23685552 Full text @ Arterioscler. Thromb. Vasc. Biol.

Objective—To elucidate the functions of sister-of-mammalian grainyhead (SOM1) and SOM3 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.