A novel Rb- and p300-binding protein inhibits transactivation by MyoD
A novel Rb- and p300-binding protein inhibits transactivation by MyoD
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DOI：
10.1128/mcb.20.23.8903-8915.2000
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发表时间：
2000-12-01
影响因子：
5.3
通讯作者：
Schneider, MD
中科院分区：
文献类型：
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作者：
MacLellan, WR;Xiao, G;Schneider, MD
视网膜母细胞瘤蛋白 (Rb) 通过调节与其 A-B 和 C 口袋相关的因子的活性来调节细胞周期和组织特异性转录。据报道，在骨骼肌中，Rb 可以调节不可逆的细胞周期退出和肌肉特异性转录。为了确定与肌肉细胞中 Rb 相互作用的因子，我们利用酵母双杂交系统，使用 Rb 的 A-B 和 C 口袋作为诱饵。我们将一种新的蛋白质命名为 EIA 样分化抑制剂 1 (EID-1)，它是分离的主要 Rb 结合克隆。它优先在成人心脏和骨骼肌中表达，编码 187 个氨基酸的蛋白质，在其 C 末端具有经典的 Rb 结合基序 (LXCXE)。骨骼肌中 EID-1 的过度表达抑制组织特异性转录。骨骼肌限制性基因的抑制是通过 MyoD 的反式激活阻断介导的，与 G(1) 退出无关，并且令人惊讶的是，抑制 EID-1 与 Rb 结合的突变会增强这种抑制。 MyoD 的抑制可能是由于 EID-1 能够结合并抑制 p300 的组蛋白乙酰化酶活性（一种重要的 MyoD 共激活剂）的能力。因此，EID-1 结合 Rb 和 p300，是一种新型的 MyoD 功能抑制剂。
The retinoblastoma protein (Rb) regulates both the cell cycle and tissue-specific transcription, by modulating the activity of factors that associate with its A-B and C pockets. In skeletal muscle, Rb has been reported to regulate irreversible cell cycle exit and muscle-specific transcription. To identify factors interacting with Rb in muscle cells, we utilized the yeast two-hybrid system, using the A-B and C pockets of Rb as bait. A novel protein we have designated EIA-like inhibitor of differentiation 1 (EID-1), was the predominant Rb-binding clone isolated. It is preferentially expressed in adult cardiac and skeletal muscle and encodes a 187-amino-acid protein, with a classic Rb-binding motif (LXCXE) in its C terminus. Overexpression of EID-1 in skeletal muscle inhibited tissue-specific transcription. Repression of skeletal muscle-restricted genes was mediated by a block to transactivation by MyoD independent of G(1) exit and, surprisingly, was potentiated by a mutation that prevents EID-1 binding to Rb. Inhibition of MyoD may be explained by EID-1's ability to bind and inhibit p300's histone acetylase activity, an essential MyoD coactivator. Thus, EID-1 binds both Rb and p300 and is a novel repressor of MyoD function.