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Originally published In Press as doi:10.1074/jbc.M108476200 on October 26, 2001

J. Biol. Chem., Vol. 277, Issue 1, 218-224, January 4, 2002
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ASB-2 Inhibits Growth and Promotes Commitment in Myeloid Leukemia Cells*

Florence C. GuibalDagger , Christel Moog-LutzDagger , Piotr Smolewski§, Yolande Di GioiaDagger , Zbigniew Darzynkiewicz§, Pierre G. LutzDagger , and Yvon E. CayreDagger ||**

From the Dagger  Unité INSERM U417, Hôpital Saint Antoine, 184 Rue du Faubourg Saint Antoine, 75012 Paris, France, the § Brander Cancer Research Institute, New York Medical College, Hawthorne, New York 10532, and the || Department of Microbiology/Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541

In acute promyelocytic leukemia (APL) cells harboring the promyelocytic leukemia retinoic acid receptor alpha  (PML-RARalpha ) chimeric protein, retinoic acid (RA)-induced differentiation is triggered through a PML-RARalpha signaling resulting in activation of critical target genes. Induced differentiation of APL cells is always preceded by withdrawal from the cell cycle and commitment events leading to terminal differentiation. Here we have identified the human ankyrin repeat-containing protein with a suppressor of cytokine signaling box-2 (ASB-2) cDNA, as a novel RA-induced gene in APL cells. PML-RARalpha strongly enhanced RA-induced ASB-2 mRNA expression. In myeloid leukemia cells, ASB-2 expression induced growth inhibition and chromatin condensation recapitulating early events critical to RA-induced differentiation of APL cells.

* This work was supported by INSERM; by CNRS; by grants from the Fondation de France, the Comité de Paris de La Ligue Contre le Cancer, the Association Pour la Recherche sur le Cancer, the Association Combattre la Leucémie, the Lady Tata Memorial Trust, the Leukemia Research Foundation; and by National Institutes of Health Grant RO-1 28704 (to Z. D.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AJ251238.

These authors should be considered as equal last authors.

** To whom correspondence should be addressed: Unité INSERM U417, Hôpital Saint Antoine, 184 Rue du Faubourg Saint Antoine, 75012 Paris, France. Tel.: 33-1-49284613; Fax: 33-1-43406837; E-mail: cayre@st-antoine.inserm.fr.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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