SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes
SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes
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DOI：
10.1016/j.molcel.2006.11.006
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发表时间：
2006-12-08
期刊：
影响因子：
16
通讯作者：
Roberts, Anita B.
中科院分区：
文献类型：
--
作者：
Fujii, Makiko;Lyakh, Lyudmila A.;Roberts, Anita B.
使用酵母双杂交筛选，我们发现 SNIP1（Smad 核相互作用蛋白 1）与细胞增殖和转化的关键调节因子 c-Myc 相关。我们证明 SNIP1 作为 c-Myc 活性的重要调节因子，通过其自己的 C 末端结合 c-Myc 的 N 末端，并且 SNIP1 通过稳定 c-Myc 免受蛋白酶体降解和桥接 c-Myc/p300 复合物来增强 c-Myc 的转录活性。 SNIP1 对 c-Myc 的这些作用可能有助于 SNIP1、c-Myc 和 H-Ras 在体外转化测定中诱导病灶形成以及支持不依赖贴壁的生长的协同作用。非小细胞肺癌组织阵列中 SNIP1 和 c-Myc 染色的显着关联进一步证明它们的活性可能存在关联，并表明 SNIP1 可能是致癌过程中 c-Myc 活性的重要调节剂。
Using a yeast two-hybrid screen, we found that SNIP1 (Smad nuclear-interacting protein 1) associates with c-Myc, a key regulator of cell proliferation and transformation. We demonstrate that SNIP1 functions as an important regulator of c-Myc activity, binding the N terminus of c-Myc through its own C terminus, and that SNIP1 enhances the transcriptional activity of c-Myc both by stabilizing it against proteosomal degradation and by bridging the c-Myc/p300 complex. These effects of SNIP1 on c-Myc likely contribute to synergistic effects of SNIP1, c-Myc, and H-Ras in inducing formation of foci in an in vitro transformation assay and also in supporting anchorage-independent growth. The significant association of SNIP1 and c-Myc staining in a non-small cell lung cancer tissue array is further evidence that their activities might be linked and suggests that SNIP1 might be an important modulator of c-Myc activity in carcinogenesis.