Transcriptional Regulation of CRD-BP by c-myc: Implications for c-myc Functions.
Transcriptional Regulation of CRD-BP by c-myc: Implications for c-myc Functions.
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DOI：
10.1177/1947601910395581
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发表时间：
2010-10-01
期刊：
影响因子：
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通讯作者：
Spiegelman, Vladimir S
中科院分区：
文献类型：
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作者：
Noubissi, Felicite K;Nikiforov, Mikhail A;Spiegelman, Vladimir S
编码区决定簇结合蛋白CRD-BP是一种多功能的RNA结合蛋白，参与不同的过程，如mRNA周转，翻译控制和定位。它主要在胎儿和新生儿组织中表达，在那里它调节正常胚胎发育所必需的许多转录物。CRD-BP在正常成人组织中很少或不存在，但在各种肿瘤和癌前肿瘤以及大多数细胞系中重新激活和/或过表达。它的表达与某些癌症的最具侵袭性的形式有关。CRD-BP是不同基因的重要调节因子，包括多种癌基因或原癌基因（c-myc、beta-TrCP 1、GLI 1等）。CRD-BP表达的调节对于正确控制其靶点至关重要，因为其过表达可能在异常细胞增殖、抑制细胞凋亡、侵袭和转移中发挥重要作用。CRD-BP表达调控机制的分子基础尚未完全阐明。在这篇文章中，我们已经确定了c-myc作为一种新的CRD-BP的转录调节因子。我们发现c-myc与CRD-BP启动子结合并诱导其转录。CRD-BP表达的这种诱导有助于c-myc通过涉及上调β-TrCP 1水平和活性以及加速PDCD 4降解的机制在调节翻译、增加细胞大小和加速细胞周期进展中发挥作用。
The coding region determinant binding protein, CRD-BP, is a multifunctional RNA binding protein involved in different processes such as mRNA turnover, translation control, and localization. It is mostly expressed in fetal and neonatal tissues, where it regulates many transcripts essential for normal embryonic development. CRD-BP is scarce or absent in normal adult tissues but reactivated and/or overexpressed in various neoplastic and preneoplastic tumors and in most cell lines. Its expression has been associated with the most aggressive form of some cancers. CRD-BP is an important regulator of different genes including a variety of oncogenes or proto-oncogenes (c-myc, beta-TrCP1, GLI1, etc.). Regulation of CRD-BP expression is critical for proper control of its targets as its overexpression may play an important role in abnormal cell proliferation, suppression of apoptosis, invasion, and metastasis. Molecular bases of the regulatory mechanisms governing CRD-BP expression are still not completely elucidated. In this article, we have identified c-myc as a novel transcriptional regulator of CRD-BP. We show that c-myc binds to CRD-BP promoter and induces its transcription. This induction of CRD-BP expression contributes to the role of c-myc in the regulation of translation, increase in cell size, and acceleration of cell cycle progression via a mechanism involving upregulation of beta-TrCP1 levels and activities and accelerated degradation of PDCD4.