Sumoylation Inhibits the Growth Suppressive Properties of Ikaros

被引:12
作者
Apostolov, Apostol [1 ]
Litim-Mecheri, Isma [1 ]
Oravecz, Attila [1 ]
Goepp, Marie [1 ]
Kirstetter, Peggy [1 ]
Marchal, Patricia [1 ]
Ittel, Antoine [2 ,3 ]
Mauvieux, Laurent [2 ,3 ]
Chan, Susan [1 ]
Kastner, Philippe [1 ,4 ]
机构
[1] Univ Strasbourg, CNRS UMR 7104, INSERM U964, IGBMC, F-67404 Illkirch Graffenstaden, France
[2] Hop Univ Strasbourg, Hematol Lab, Strasbourg, France
[3] Univ Strasbourg, Fac Med Strasbourg, Federat Med Translat Strasbourg, Inst Hematol & Immunol,Lab Hematol Cellulaire,EA, Strasbourg, France
[4] Univ Strasbourg, Fac Med, Strasbourg, France
关键词
ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-BINDING PROTEINS; SUMO-1; MODIFICATION; TRANSCRIPTIONAL ACTIVITY; CELL-LINE; T-CELLS; ACTIVATION; PHOSPHORYLATION; LOCALIZATION; TRANSITION;
D O I
10.1371/journal.pone.0157767
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Ikaros transcription factor is a tumor suppressor that is also important for lymphocyte development. How post-translational modifications influence Ikaros function remains partially understood. We show that Ikaros undergoes sumoylation in developing T cells that correspond to mono-, bi- or poly-sumoylation by SUMO1 and/or SUMO2/3 on three lysine residues (K58, K240 and K425). Sumoylation occurs in the nucleus and requires DNA binding by Ikaros. Sumoylated Ikaros is less effective than unsumoylated forms at inhibiting the expansion of murine leukemic cells, and Ikaros sumoylation is abundant in human B-cell acute lymphoblastic leukemic cells, but not in healthy peripheral blood leukocytes. Our results suggest that sumoylation may be important in modulating the tumor suppressor function of Ikaros.
引用
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页数:12
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