RSUME, a Small RWD-Containing Protein, Enhances SUMO Conjugation and Stabilizes HIF-1α during Hypoxia
RSUME, a Small RWD-Containing Protein, Enhances SUMO Conjugation and Stabilizes HIF-1α during Hypoxia
SUMO conjugation to proteins is involved in the regulation of diverse cellular functions. We have identified a protein, RWD-containing sumoylation enhancer (RSUME), that enhances overall SUMO-1, -2, and -3 conjugation by interacting with the SUMO conjugase Ubc9. RSUME increases noncovalent binding of SUMO-1 to Ubc9 and enhances Ubc9 thioester formation and SUMO polymerization. RSUME enhances the sumoylation of IkB in vitro and in cultured cells, leading to an inhibition of NF-kB transcriptional activity. RSUME is induced by hypoxia and enhances the sumoylation of HIF-1alpha, promoting its stabilization and transcriptional activity during hypoxia. Disruption of the RWD domain structure of RSUME demonstrates that this domain is critical for RSUME action. Together, these findings point to a central role of RSUME in the regulation of sumoylation and, hence, several critical regulatory pathways in mammalian cells.
- Facultad de Ciencias Agrarias y Forestales Argentina
- Max Planck Institute of Psychiatry Germany
- National Scientific and Technical Research Council Argentina
- Max Planck Society Germany
- Max Planck Institute for Biology Germany
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animal cell, protein binding, I kappa B, Chlorocebus aethiops, rat, Tumor, sumoylation, article, NF-kappa B, protein domain, sumo 2 protein, Cell Hypoxia, unclassified drug, I-kappa B Kinase, immunoglobulin enhancer binding protein, priority journal, protein stability, Organ Specificity, polymerization, protein protein interaction, Mammalia, Small Ubiquitin-Related Modifier Proteins, Hypoxia-Inducible Factor 1, SUMO protein, conjugation, Protein Binding, regulatory mechanism, PROTEINS, Ubiquitin-Conjugating Enzyme UBC9, Molecular Sequence Data, SUMO-1 Protein, protein Ubc9, alpha Subunit, Cell Line, Cercopithecus aethiops, Cell Line, Tumor, Animals, Humans, controlled study, hypoxia inducible factor 1alpha, human, Amino Acid Sequence, cell protein, protein structure, protein expression, Ubiquitins, mouse, nonhuman, Base Sequence, hypoxia, Biochemistry, Genetics and Molecular Biology(all), human cell, genetic transcription, nucleotide sequence, protein RSUME, Hypoxia-Inducible Factor 1, alpha Subunit, sumo 3 protein, Ubiquitin-Conjugating Enzymes, cell function, CELLBIO, mammal cell, SUMO 1 protein, Transcription Factors
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