CRD-BP
The mouse Coding Region Determinant-Binding Protein (CRD-BP) is an RNA-binding protein.[1] CRD-BP belongs to a family of RNA binding proteins that show close a relation to the chicken β-actin zipcode-binding protein ZBP1[1] and the human forms of the protein IMP-1, IMP-2 and IMP-3.[1][2][3] Because of their close relationship, CRD-BP and its orthologs are thought to share the same biochemical properties. Upon binding to its transcripts, CRD-BP plays a role in translation by stabilizing and localizing the transcripts in the cell.[3] Normal expression of CRD-BP has been seen in the early development of the embryo.[3] Conversely, CRD-BP expression in adult tissue is extremely low or completely absent.[4]
Structure[edit]
CRD-BP is a 577 amino acid protein that contains 4 KH domains, 2 RRMs and a RGG box (Figure 2).[1] CRD-BP and human IMP-1 are not identical but shows a high degree of resemblance. They are very closely related to IMP-2, which has been determined through phylogenetic analysis (Figure 1).[3] As a result of this close phylogeny, the structure of the conserved functional domains is shared between CRD-BP, ZBP1 and the human IMPs (Figure 2).[3][5] The conserved KH domains are shared throughout the orthologs and they are able to form dimers which orient the RNA binding regions in a polar opposite manner (Figure 3A).[5] This orientation creates room for each G-X-X-G motif (Figure 3B) of each KH domain to bind its RNA transcript (Figure 3A).[5]
CRD-BP RNA transcripts[edit]
CRD-BP and its orthologs have been shown to have the ability to bind CD44, beta-actin, c-myc, IGF2, H19 and tau RNA transcripts.[6] CRD-BP has been shown to play a crucial role in cancer growth and invasion of tissues. CD44 proteins belong to a family of cell surface adhesion molecules that are involved in both cell-cell and cell-matrix communications.[7] CRD-BP binds to and protects CD44 RNA which shows increased expression in cancers.[6] CRD-BP plays a role in the localization of β-actin mRNA by binding to the localization element in the 3'UTR region.[8] Aberrant expression of the oncogenic c-myc gene has been shown in the formation of tumours.[1] c-myc mRNA contains a coding region instability determinant (CRD) which CRD-BP has been shown to bind, therefore, protecting c-myc mRNA from endonucleolytic attack.[1] CRD-BP also binds IGF2 and H19 mRNA.[8] The H19 gene is located downstream of the IGF2 on chromosome 11 and chromosome 7 on humans and mice, respectively.[8] The binding of CRD-BP to these transcripts has shown to alter the expression of the genes. The microtubule-associated protein (MAP) is coded for by tau mRNA and is mainly found in the axon of neurons.[8] The 3’UTR of tau mRNA contains a cis-regulatory element that controls the axonal localization of tau mRNA.[8] CRD-BP binds to the axonal localization signal (ALS) of tau and plays a role in the localization of the transcript.[8]
CRD-BP, therefore, has been shown to be upregulated in many diseases, including cancers.
References[edit]
- ^ a b c d e f Doyle, G., et al. 1998. The c-myc¬ coding region determinant-binding protein: a member of a family of KH domain RNA-binding proteins. Nuc. Acid. Res. 26:5036-5044.
- ^ Liao, B., et al. 2005. The RNA-binding protein IMP-3 is a translational activator of insulin-growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells. The journal of biological chemistry, 280: 18517-18524
- ^ a b c d e Christiansen, J., et al. 2009. IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes. Journal of Molecular Endocrinology, 43:187-195
- ^ Prokipcak, R., et al. 1994. Purification and properties of a protein that binds to the C-terminal coding region of human c-myc mRNA. Journal of Biological Chemistry, 12: 9261-9269.
- ^ a b c Chao,J., et al. 2010. ZBP1 recognition of β-actin zipcode induces RNA looping. Genes Dev, 24: 148-158.
- ^ a b Vikesaa, J., et al. 2006. RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO 25: 1456-1468.
- ^ Goodison, S., et al. 1999. CD44 Cell adhesion molecules. Mol Path, 52: 189-196.
- ^ a b c d e f Ioannidis, P., and T. Trangas., 2006. CRD-BP/IMP1: An RNA Binding Protein with Tumorigenic Characteristics. Trends in RNA Research. pp. 39-71.