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Published online before print August 3, 2004

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(Journal of Leukocyte Biology. 2004;76:1082-1088.)
© 2004 by Society for Leukocyte Biology

The orphan nuclear receptor SHP is involved in monocytic differentiation, and its expression is increased by c-Jun

Yoon Ha Choi^*, Min Jung Park^*, Kook Whan Kim^*, Hyung Chul Lee^*, Young Hyun Choi and JaeHun Cheong^*,1

^* Department of Molecular Biology, Pusan National University, Busan, Korea; and
Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, Korea

¹ Correspondence: Department of Molecular Biology, Pusan National University, Busan 607-935, Korea. E-mail: molecule85{at}pusan.ac.kr

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.

Key Words: monocyte • c-Jun • SHP

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