ASB-2 inhibits growth and promotes commitment in myeloid leukemia cells.
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.
Guibal
Florence C
FC
Unité INSERM U417, Hôpital Saint Antoine, 184 Rue du Faubourg Saint Antoine, 75012 Paris, France.
Moog-Lutz
Christel
C
Smolewski
Piotr
P
Di Gioia
Yolande
Y
Darzynkiewicz
Zbigniew
Z
Lutz
Pierre G
PG
Cayre
Yvon E
YE
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D050826:Suppressor of Cytokine Signaling Proteins; D014212:Tretinoin / Q000494:pharmacology
C437987:ASB2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002843:Chromatin; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D050826:Suppressor of Cytokine Signaling Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin