ATRA-regulated Asb-2 gene induced in differentiation of HL-60 leukemia cells

Suppressors of cytokine signaling (SOCS) proteins possess common structures , a SOCS box at the C-terminus and a SH2 domain at their center. These supp ressors are inducible in response to cytokines and act as negative regulato rs of cytokine signaling. The ASB proteins also contain the SOCS box and th e 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 gen e inducers have been identified. In this study, we screened the specific ge nes expressed in the course of differentiation of HL-60 cells, and demonstr ated that ASB-2, one of the ASB proteins, was rapidly induced by all-trans retinoic acid (ATRA). Typical retinoid receptors (RA Rs) or retinoid X rece ptors (RXRs) binding element (RARE/RXRE) were presented in the promoter of the Asb-2 gene. We showed that RAR alpha, one of the RARs, binds to the RAR E/RXRE in the Asb-2 promoter. In addition, we demonstrated by luciferase re porter assay that this element was a functional RARE/RXRE. These findings i ndicate that ASB-2 is directly induced by ATRA and may act as a significant regulator, underlying such physiological processes as cell differentiation . (C) 2001 Federation of European Biochemical Societies. Published by Elsev ier Science B.V. All rights reserved.