ASB-2 Inhibits Growth and Promotes Commitment in Myeloid Leukemia Cells

• Published in: The Journal of biological chemistry 2002-01, Vol.277 (1), p.218-224
• Main Authors: Guibal, Florence C., Moog-Lutz, Christel, Smolewski, Piotr, Di Gioia, Yolande, Darzynkiewicz, Zbigniew, Lutz, Pierre G., Cayre, Yvon E.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Base Sequence; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell Differentiation - drug effects; Chromatin - metabolism; Humans; Leukemia, Promyelocytic, Acute - pathology; Life Sciences; Molecular Sequence Data; Neoplasm Proteins - physiology; Oncogene Proteins, Fusion - physiology; RNA, Messenger - analysis; Suppressor of Cytokine Signaling Proteins; Tretinoin - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M108476200

In acute promyelocytic leukemia (APL) cells harboring the promyelocytic leukemia retinoic acid receptor α (PML-RARα) chimeric protein, retinoic acid (RA)-induced differentiation is triggered through a PML-RARα 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-RARα 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.