TRIM24 mediates ligand-dependent activation of androgen receptor and is repressed by a bromodomain-containing protein, BRD7, in prostate cancer cells.
The androgen receptor (AR) is a ligand-dependent transcription factor that belongs to the family of nuclear receptors, and its activity is regulated by numerous AR coregulators. AR plays an important role in prostate development and cancer. In this study, we found that TRIM24/transcriptional intermediary factor 1alpha (TIF1alpha), which is known as a ligand-dependent nuclear receptor co-regulator, interacts with AR and enhances transcriptional activity of AR by dihydrotestosterone in prostate cancer cells. We showed that TRIM24 functionally interacts with TIP60, which acts as a coactivator of AR and synergizes with TIP60 in the transactivation of AR. We also showed that TRIM24 binds to bromodomain containing 7 (BRD7), which can negatively regulate cell proliferation and growth. A luciferase assay indicated that BRD7 represses the AR transactivation activity upregulated by TRIM24. These findings indicate that TRIM24 regulates AR-mediated transcription in collaboration with TIP60 and BRD7.
Kikuchi
Misato
M
Department of Biochemistry, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Okumura
Fumihiko
F
Tsukiyama
Tadasuke
T
Watanabe
Masashi
M
Miyajima
Naoto
N
Tanaka
Junji
J
Imamura
Masahiro
M
Hatakeyama
Shigetsugu
S
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D000074443:Lysine Acetyltransferase 5; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
D000728:Androgens; D002868:Chromosomal Proteins, Non-Histone; D013196:Dihydrotestosterone; D051548:Histone Acetyltransferases; D008024:Ligands; D000074443:Lysine Acetyltransferase 5; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C400206:Brd7 protein, mouse; C093517:transcriptional intermediary factor 1; C098489:KAT5 protein, human; C523065:Kat5 protein, mouse