ASB2 is an elongin BC-interacting protein that can assemble with cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex
ASB2 is an elongin BC-interacting protein that can assemble with cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex
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DOI：
10.1074/jbc.m413040200
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发表时间：
2005-02-18
影响因子：
4.8
通讯作者：
Lutz, PG
中科院分区：
文献类型：
--
作者：
Heuzé, ML;Guibal, FC;Lutz, PG
The ankyrin repeat-containing protein with a suppressor of cytokine signaling box-2 (ASB2) gene was identified as a retinoic acid-response gene and a target of the promyelocytic leukemia-retinoic acid receptor-a oncogenic protein characteristic of acute promyelocytic leukemia. AS132 在骨髓性白血病细胞中的表达可抑制生长并促进定型，重现已知对分化至关重要的早期步骤。在这里，我们表明 AS132 通过与 Elongin BC 复合物相互作用，可以与 Cullin5-Rbxl 组装形成 E3 泛素连接酶复合物，刺激 E2 泛素缀合酶 Ubc5 的多泛素化。这是首次表明 ASB 蛋白家族成员 AS132 是 ECS（Elongin C-Cullin-SOCS 盒）型 E3 泛素连接酶复合物的亚基。总而言之，我们的结果强烈表明，AS132 靶向特定蛋白质，使其被诱导分化的白血病细胞中的蛋白酶体破坏。
The ankyrin repeat-containing protein with a suppressor of cytokine signaling box-2 (ASB2) gene was identified as a retinoic acid-response gene and a target of the promyelocytic leukemia-retinoic acid receptor-a oncogenic protein characteristic of acute promyelocytic leukemia. Expression of AS132 in myeloid leukemia cells inhibits growth and promotes commitment, recapitulating an early step known to be critical for differentiation. Here we show that AS132, by interacting with the Elongin BC complex, can assemble with Cullin5-Rbxl to form an E3 ubiquitin ligase complex that stimulates polyubiquitination by the E2 ubiquitin-conjugating enzyme Ubc5. This is a first indication that a member of the ASB protein family, AS132, is a subunit of an ECS (Elongin C-Cullin-SOCS box)-type E3 ubiquitin ligase complex. Altogether, our results strongly suggest that AS132 targets specific proteins to destruction by the proteasome in leukemia cells that have been induced to differentiate.