MSSP promotes ras/myc cooperative cell transforming activity by binding to c-Myc
MSSP promotes ras/myc cooperative cell transforming activity by binding to c-Myc
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DOI：
10.1046/j.1365-2443.2000.00311.x
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发表时间：
2000-02-01
期刊：
影响因子：
2.1
通讯作者：
Ariga, H
中科院分区：
文献类型：
--
作者：
Niki, T;Izumi, S;Ariga, H
背景：MSSP（myc 单链结合蛋白）最初被鉴定为识别人类 c-Myc 基因中假定的复制起点/转录增强子的蛋白质。克隆了编码四个家族蛋白 MSSP-1、MSSP-2、Scr2 和 Scr3 的 cDNA。这些蛋白质携带两个拷贝的假定 RNA 结合域 RNP-A 和 RNP-B，并被认为参与 DNA 复制和从 G(1) 到 S 期的细胞周期进程。 结果：我们报告 MSSP-1 和 MSSP-2 与 Max 并排直接结合到 c-Myc 的 C 端部分。 MSSP、c-Myc和Max在体内形成三元复合物，尽管MSSP并不直接与Max结合。 MSSP/Myc/Max三元复合物失去了与E-box序列（c-Myc/Max复合物的识别序列）的结合活性，从而消除了c-Myc的E-box依赖性转录活性。 MSSP 以依赖于 RNP 序列的方式特异性刺激 c-myc 与 ras 的协同转化活性，而 mssp 本身在小鼠 NIH3T3 细胞中没有表现出转化活性。与 ras 加 myc 或单独 ras 的转化体相比，NIH3T3 转化体与 ras、myc 和 mssp 一起在软琼脂中生长形成非常大的菌落。结论：MSSP 是 c-Myc 的调节剂，c-Myc/MSSP 复合物可能会解除细胞周期控制的调节并导致细胞走向转化途径。
Background: MSSPs, myc single strand binding proteins, were originally identified as proteins recognizing a putative replication origin/transcriptional enhancer in the human c-Myc gene. The cDNAs encoding four of the family proteins, MSSP-1, MSSP-2, Scr2 and Scr3, were cloned. These proteins carry two copies of the putative RNA binding domains, RNP-A and RNP-B, and have been suggested to participate in DNA replication and cell cycle progression from the G(1) to the S phase.Results: We report that MSSP-1 and MSSP-2 bound directly to the C-terminal portion of c-Myc, along with Max, side by side. MSSP, c-Myc and Max formed a ternary complex in vivo, although MSSP did not directly associate with Max. The MSSP/Myc/Max ternary complex lost the binding activity to the E-box sequence-the recognition sequence of c-Myc/Max complex-thereby abrogating the E-box-dependent transcription activity of c-Myc. MSSP specifically stimulated the cooperative transforming activity of c-myc with ras, in a manner dependent upon the RNP sequences, while mssp itself showed no transforming activity in mouse NIH3T3 cells. The NIH3T3 transformants, together with ras, myc and mssp, grew to form very large colonies in soft agar, as compared to those with ras plus myc or ras alone.Conclusions: MSSP is a modulator of c-Myc and the c-Myc/MSSP complex may deregulate cell cycle controls and lead cells towards transforming pathways.