Coordinated regulation of AIB1 transcriptional activity by sumoylation and phosphorylation.
AIB1, a member of the steroid receptor coactivator (SRC) family that participates in gene transcriptional activation by nuclear receptors and other transcription factors, is required for animal growth and reproductive development and implicated in breast carcinogenesis. The mechanisms underlying the AIB1 pleiotropic functions are not fully understood and neither is the regulation of its activity. Here, we showed that AIB1 was a sumoylated protein and the sumoylation attenuated the transactivation activity of AIB1, which is in contrast to the sumoylation of its paralogs, GRIP1 and SRC-1. The transactivation activity of AIB1 is enhanced by its phosphorylation by several kinases, including mitogen-activated protein kinase. We demonstrated in this report that estrogen treatment led to an increased phosphorylation and decreased sumoylation of AIB1 and that the sumoylation coordinated with phosphorylation in regulating the transcriptional activity of AIB1, providing a mechanism for post-translational modifications in regulating the transcriptional output of AIB1.
Wu
Huijian
H
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Sun
Luyang
L
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Zhang
Ying
Y
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Chen
Yupeng
Y
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Shi
Bin
B
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Li
Ruifang
R
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Wang
Yan
Y
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Liang
Jing
J
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Fan
Dongwei
D
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Wu
Ge
G
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Wang
Dan
D
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Li
Shaosi
S
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Shang
Yongfeng
Y
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China. Electronic address: yshang@hsc.pku.edu.cn.
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004967:Estrogens / Q000494:pharmacology; D051548:Histone Acetyltransferases; D006801:Humans; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D056921:Nuclear Receptor Coactivator 3; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
D004967:Estrogens; D025842:SUMO-1 Protein; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; D010770:Phosphotransferases