The orphan nuclear receptor SHP is involved in monocytic differentiation, and its expression is increased by c-Jun.
Small heterodimer partner (SHP) is an atypical member of nuclear receptor superfamily that lacks a DNA binding domain. Here, we show that SHP expression increases during monocytic differentiaton with exposure HL-60 leukemia cells to a 12-O-tetradecanoylphorbol-13-acetate (TPA) response element, whose treatment induced the SHP promoter activity dependent on c-Jun expression, which is well known to be involved in the commitment step in the TPA-induced differentiation of HL-60 leukemia cells. We also show that overexpression and activation signaling of c-Jun increase the SHP promoter activity, suggesting that the level of SHP expression is normally limiting for c-Jun-dependent monocytic differentiation. Electrophoretic mobility shift assays using oligonucleotides derived from the SHP promoter reveal that c-Jun exhibit TPA-induced DNA binding, providing a mechanism for the transcriptional activation of SHP gene expression. It was also found that overexpression of SHP and c-Jun greatly facilitated monocytic differentiation by TPA and surprisingly, that expression of SHP or c-Jun alone was sufficient to make cells differentiate into functionally mature monocytes, but silencing of SHP and c-Jun by RNA interference diminished the TPA-induced monocytic differentiation. Taken together, these works suggest that c-Jun works to activate the expression of SHP genes associated with the cascade regulation of monocytic differentiation.
Choi
Yoon Ha
YH
Department of Molecular Biology, Pusan National University, Busan, Korea.
Park
Min Jung
MJ
Kim
Kook Whan
KW
Lee
Hyung Chul
HC
Choi
Young Hyun
YH
Cheong
Jaehun
J
D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D004247:DNA; D013755:Tetradecanoylphorbol Acetate