Induction of Rb-associated protein (RbAp46) by Wilms' tumor suppressor WT1 mediates growth inhibition
Induction of Rb-associated protein (RbAp46) by Wilms' tumor suppressor WT1 mediates growth inhibition
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DOI：
10.1074/jbc.273.42.27047
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发表时间：
1998-10-16
影响因子：
4.8
通讯作者：
Wang, ZY
中科院分区：
文献类型：
--
作者：
Guan, LS;Rauchman, M;Wang, ZY
Wilms肿瘤抑制基因wt1编码锌指转录因子WT1，其在控制泌尿生殖系统发育中起重要作用。以前，WT1已被证明能抑制细胞生长，并抑制由许多生长促进基因的启动子启动的转录。然而，很少有生理靶基因的转录激活WT1已经建立。使用抑制性消减杂交聚合酶链反应，我们分离出WT1的靶基因，该基因在表达WT1的细胞中上调约15倍。该基因被鉴定为视网膜母细胞瘤抑制因子（Rb）相关蛋白46（RbAp46），这是一种与Rb发生物理相互作用的核蛋白，是人类mSin3辅助抑制因子复合物的组成部分。转染RbAp46 cDNA的细胞比对照细胞形成更少的集落，并且RbAp46抑制转染细胞的生长速率（约a倍）。在发育中的肾脏和性腺中，RbAp46表现出与WT1相似的表达模式。我们的结论是，RbAp46具有较强的生长抑制活性，并可能作为WT1的功能的重要介质。
The Wilms' tumor suppressor gene, wt1, encodes a zinc-finger transcription factor, WT1, that plays an important role in controlling urogenital development. Previously, WT1 has been shown to inhibit cell growth and to repress transcription initiated from the promoters of a number of growth-promoting genes. However, few physiological target genes that are transcriptionally activated by WT1 have been established. Using suppression subtractive hybridization polymerase chain reaction, we isolated a WT1 target gene that is up-regulated about 15-fold in cells expressing WT1. The gene was identified as retinoblastoma suppressor (Rb)-associated protein 46 (RbAp46), a nuclear protein that interacts physically with Rb and is a component of the human mSin3 co-repressor complex. Cells transfected with RbAp46 cDNA formed fewer colonies than the control cells, and RbAp46 suppressed the growth rate (by about a-fold) of transfected cells. In the developing kidney and gonad, RbAp46 exhibits an expression pattern similar to that of WT1. We conclude that RbAp46 has strong growth inhibition activity and may function as an important mediator of WT1's function.