Noubissi Felicite K, Nikiforov Mikhail A, Colburn Nancy, Spiegelman Vladimir S
Department of Dermatology and Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Genes Cancer. 2010 Oct;1(10):1074-82. doi: 10.1177/1947601910395581.
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, β-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 β-TrCP1 levels and activities and accelerated degradation of PDCD4.
编码区决定簇结合蛋白（CRD - BP）是一种多功能RNA结合蛋白，参与mRNA周转、翻译控制和定位等不同过程。它主要在胎儿和新生儿组织中表达，在这些组织中调节许多对正常胚胎发育至关重要的转录本。CRD - BP在正常成人组织中稀少或不存在，但在各种肿瘤性和癌前肿瘤以及大多数细胞系中被重新激活和/或过度表达。其表达与某些癌症的最侵袭性形式相关。CRD - BP是包括多种癌基因或原癌基因（c - myc、β - TrCP1、GLI1等）在内的不同基因的重要调节因子。CRD - BP表达的调节对于其靶标的适当控制至关重要，因为其过表达可能在异常细胞增殖、细胞凋亡抑制、侵袭和转移中起重要作用。控制CRD - BP表达的调节机制的分子基础仍未完全阐明。在本文中，我们已确定c - myc是CRD - BP的一种新型转录调节因子。我们表明c - myc与CRD - BP启动子结合并诱导其转录。CRD - BP表达的这种诱导通过涉及β - TrCP1水平和活性上调以及PDCD4加速降解的机制，有助于c - myc在翻译调节、细胞大小增加和细胞周期进程加速中的作用。
