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ATRA‐regulated Asb‐2 gene induced in differentiation of HL‐60 leukemia cells
Author(s) -
Kohroki Junya,
Fujita Sayaka,
Itoh Norio,
Yamada Yukiko,
Imai Harue,
Yumoto Noboru,
Nakanishi Tsuyoshi,
Tanaka Keiichi
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02829-0
Subject(s) - retinoic acid , biology , retinoid , reporter gene , response element , retinoid x receptor , microbiology and biotechnology , gene , cellular differentiation , receptor , transcription factor , promoter , nuclear receptor , biochemistry , gene expression
Suppressors of cytokine signaling (SOCS) proteins possess common structures, a SOCS box at the C‐terminus and a SH2 domain at their center. These suppressors are inducible in response to cytokines and act as negative regulators of cytokine signaling. The ASB proteins also contain the SOCS box and the ankyrin repeat sequence at the N‐terminus, but do not have the SH2 domain. Although Socs genes are directly induced by several cytokines, no Asb gene inducers have been identified. In this study, we screened the specific genes expressed in the course of differentiation of HL‐60 cells, and demonstrated that ASB‐2, one of the ASB proteins, was rapidly induced by all‐ trans retinoic acid (ATRA). Typical retinoid receptors (RARs) or retinoid X receptors (RXRs) binding element (RARE/RXRE) were presented in the promoter of the Asb‐2 gene. We showed that RARα, one of the RARs, binds to the RARE/RXRE in the Asb‐2 promoter. In addition, we demonstrated by luciferase reporter assay that this element was a functional RARE/RXRE. These findings indicate that ASB‐2 is directly induced by ATRA and may act as a significant regulator, underlying such physiological processes as cell differentiation.