title: Hypoxia reduces MAX expression in endothelial cells by unproductive splicing.
abstract: The MYC-MAX-MXD network is involved in the regulation of cell differentiation and proliferation. Hypoxia affects the expression levels of several members of this network, but changes specific to MAX expression have so far not been shown. We found that in endothelial cells, hypoxia induces alternative splicing of MAX, thereby increasing the expression of two MAX isoforms that differ from the wild type in their 3' end. Isoform C is degraded by nonsense-mediated decay and isoform E encodes a highly unstable protein. The instability of isoform E is conferred by 36 isoform-specific amino acids, which have the capacity to destabilize heterologous proteins. Both splicing events are therefore unproductive and serve the purpose to downregulate the wild type protein.
authors.affiliation: Department of Biology, Technical University Darmstadt, Schnittspahnstr. 10, 64287 Darmstadt, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kemmerer
authors.affiliation: Department of Biology, Technical University Darmstadt, Schnittspahnstr. 10, 64287 Darmstadt, Germany. Electronic address: weigand@bio.tu-darmstadt.de.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Weigand
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000235:genetics*; D015687:Cell Hypoxia / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D008969:Molecular Sequence Data; D059365:Nonsense Mediated mRNA Decay; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C067850:Myc associated factor X; D020033:Protein Isoforms; D012333:RNA, Messenger
keywords: Alternative splicing; Hypoxia; MYC; MYC associated factor X; Nonsense-mediated decay; Protein stability