Repression of SOX6 transcriptional activity by SUMO modification.
SOX6 plays key functions in several developmental processes, including neurogenesis and skeleton formation. In this report, we show that SOX6 is modified in vitro and in vivo by small ubiquitin-related modifier (SUMO) on two distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a SUMO protease increased SOX6 transcriptional activity. Furthermore, co-expression of SOX6 with SUMO2 results in the appearance of SOX6 in a punctate nuclear pattern that colocalized with promyelocytic leukemia protein, which was partially abolished by mutations in SOX6 sumoylation sites.
Fernández-Lloris
R
R
Departament de Ciències Fisiològiques II, IDIBELL, Campus de Bellvitge, Universitat de Barcelona, C/Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Spain.
Osses
N
N
Jaffray
E
E
Shen
L N
LN
Vaughan
O A
OA
Girwood
D
D
Bartrons
R
R
Rosa
J L
JL
Hay
R T
RT
Ventura
F
F
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D055755:SOXD Transcription Factors; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000502:physiology; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C486270:SOX6 protein, human; D055755:SOXD Transcription Factors; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9