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The orphan nuclear receptor SHP is involved in monocytic differentiation, and its expression is increased by c‐Jun
Author(s) -
Choi Yoon Ha,
Park Min Jung,
Kim Kook Whan,
Lee Hyung Chul,
Choi Young Hyun,
Cheong JaeHun
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1203658
Subject(s) - small heterodimer partner , biology , electrophoretic mobility shift assay , monocytic leukemia , gene silencing , microbiology and biotechnology , cellular differentiation , acute monocytic leukemia , nuclear receptor , transcription factor , cancer research , cell culture , gene , biochemistry , genetics
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.