Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors.
Small ubiquitin-like modifier (SUMO) modification has emerged as an important posttranslational control of protein functions. Daxx, a transcriptional corepressor, was reported to repress the transcriptional potential of several transcription factors and target to PML oncogenic domains (PODs) via SUMO-dependent interactions. The mechanism by which Daxx binds to sumoylated factors mediating transcriptional and subnuclear compartmental regulation remains unclear. Here, we define a SUMO-interacting motif (SIM) within Daxx and show it to be crucial for targeting Daxx to PODs and for transrepression of several sumoylated transcription factors, including glucocorticoid receptor (GR). In addition, the capability of Daxx SIM to bind SUMO also controls Daxx sumoylation. We further demonstrate that arsenic trioxide-induced sumoylation of PML correlates with a change of endogenous Daxx partitioning from GR-regulated gene promoter to PODs and a relief of Daxx repression on GR target gene expression. Our results provide mechanistic insights into Daxx in SUMO-dependent transcriptional control and subnuclear compartmentalization.
Lin
Ding-Yen
DY
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, Republic of China.
Huang
Yen-Sung
YS
Jeng
Jen-Chong
JC
Kuo
Hong-Yi
HY
Chang
Che-Chang
CC
Chao
Ting-Ting
TT
Ho
Chun-Chen
CC
Chen
Yun-Ching
YC
Lin
Tong-Ping
TP
Fang
Hsin-I
HI
Hung
Chih-Chang
CC
Suen
Ching-Shu
CS
Hwang
Ming-Jing
MJ
Chang
Kun-Sang
KS
Maul
Gerd G
GG
Shih
Hsiu-Ming
HM
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D056970:Co-Repressor Proteins; D003907:Dexamethasone / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001152:Arsenicals; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010087:Oxides; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D003907:Dexamethasone; D000077237:Arsenic Trioxide