Interaction of the developmental regulator SALL1 with UBE2I and SUMO-1.
Mutations in the SALL1 gene on chromosome 16q12.1 cause Townes-Brocks syndrome (TBS). This autosomal dominantly inherited disorder is characterized by typical malformations of the thumbs, the ears, and the anus, and also commonly affects the kidneys and other organ systems. SALL1 has recently been shown to localize to chromocenters and other heterochromatin foci in murine fibroblasts and to interact with the telomere-repeat-binding factor TRF1/PIN2. Here, we show that the ubiquitin-conjugating enzyme 2I (UBE2I), the human homolog of S. cerevisiae UBC9, and the small ubiquitin-like modifier-1 (SUMO-1) interact with SALL1 in the yeast two-hybrid system. The interaction of SALL1 and UBE2I was confirmed in a glutathione S-transferase (GST) pull-down experiment. In an in vitro assay, it could be demonstrated that SALL1 is covalently modified by at least two SUMO-1 molecules in the presence of UBA2/AOS1 and UBE2I. Mutation of lysine 1086 of SALL1 to arginine abrogates SALL1 sumoylation, suggesting the presence of a polymeric SUMO-1 chain in the wild type state.
Institute of Human Genetics, University of Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany.
Christian
C
Netzer
Stefan K
SK
Bohlander
Leonie
L
Rieger
Stefan
S
Müller
Jürgen
J
Kohlhase
D000015:Abnormalities, Multiple / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D005799:Genes, Dominant; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008938:Mitosis; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D025842:SUMO-1 Protein / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013577:Syndrome; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes; D001616:beta-Galactosidase / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D002352:Carrier Proteins; D018076:DNA, Complementary; C104146:SALL1 protein, human; D025842:SUMO-1 Protein; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; D005982:Glutathione Transferase; D001616:beta-Galactosidase; D008025:Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9