Disease relevance of IGF2BP1

• IMP mRNA expression levels might play an important role in ovarian cancer development and progression, and IMP-1 overexpression is a prognostic marker for patients with ovarian cancer [1].
• The mean value of the relative IMP-1 mRNA expression ratio was significantly higher in both ovarian cancer and adenoma samples compared to normal ovarian samples (p<0.05) [1].
• The glioma lines also secreted various amounts of two smaller inhibitors of metalloproteinases (IMPs), also seen in rabbit brain capillary endothelial cell CM (IMP-1 at Mr 22,000 and IMP-2 at Mr 19,000), and an inhibitor not previously identified (IMP-3 at Mr 16,500) [2].
• 8q24 Copy number gains and expression of the c-myc mRNA stabilizing protein CRD-BP in primary breast carcinomas [3].
• The highest frequency (60%) of CRD-BP positive tumors was observed in meningiomas, either benign (11/18) or atypical (3/3) [4].

Psychiatry related information on IGF2BP1

• Using this method, we found that the fragile X mental retardation protein (FMRP) isoform 18 and the human zipcode-binding protein 1 ortholog IMP1, an RNA transport factor, were present on common mRNAs [5].

High impact information on IGF2BP1

• In contrast to most other organs, intestinal epithelial cells continue to express IMP1 postnatally, and Imp1(-/-) mice exhibited impaired development of the intestine, with small and misshapen villi and twisted colon crypts [6].
• Taken together, the results demonstrate that IMP1 is essential for normal growth and development [6].
• However, it was unclear why a CRD-BP is required to protect a well-translated mRNA whose coding region is covered with ribosomes [7].
• CRD-BP/IMP1 expression characterizes cord blood CD34+ stem cells and affects c-myc and IGF-II expression in MCF-7 cancer cells [8].
• CRD-BP/IMP1 was detected only in cord blood-derived CD34(+) stem cells and not in any other cell type of either adult or cord blood origin [8].

Chemical compound and disease context of IGF2BP1

• Imipenem-resistant Pseudomonas aeruginosa producing IMP-1 metallo-beta-lactamases and lacking the outer-membrane protein OprD [9].

Biological context of IGF2BP1

• Furthermore, by applying the short interfering RNA methodology in MCF-7 cells, we observed, subsequent to knocking down CRD-BP/IMP1, decreased c-myc expression, increased IGF-II mRNA levels, and reduced cell proliferation rates [8].
• The c-myc mRNA coding region determinant-binding protein (CRD-BP) was first identified as a masking protein that stabilizes c-myc mRNA in a cell-free mRNA degradation system [10].
• By using K562 leukemia cells as a model, we show that CRD-BP gene silencing by RNA interference significantly promoted proliferation, indicating an inhibitory effect of CRD-BP on proliferation [10].
• The coding region determinant binding protein (CRD-BP) was isolated by virtue of its high affinity to the c-myc mRNA coding region stability determinant and shown to shield this message from nucleolytic attack, prolonging its half-life [3].
• CRD-BP expression was detected in 58.5% (69/118) of tumors, implying mechanisms of activation alternative to gene amplification [3].

Anatomical context of IGF2BP1

• Adult BM CD34(+) cells cultured in the presence of 5'-azacytidine expressed de novo CRD-BP/IMP1, suggesting that epigenetic modifications may be responsible for its silencing in adult non-expressing cells [8].
• Thus, we have identified a dominant function for CRD-BP in cell proliferation of human K562 cells, involving a possible IGF-II-dependent mechanism that appears independent of its ability to serve as a c-myc mRNA masking protein [10].
• Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA and that it is predominantly expressed in fetal tissues [11].
• Moreover, hCRD-BP/IMP-1 expression was detected in cell lines of neoplastic origin and in selected primary tumors [11].
• The ZBP1 then forms a ribonucleoprotein particle and moves in a myosin-dependent fashion by using the cytoskeleton for directional transport [12].

Associations of IGF2BP1 with chemical compounds

• Significant associations were detected between CRD-BP expression and the absence of estrogen receptors (p = 0.005) and between the presence of 8q24 gains and an increased number of genomic changes as measured by CGH (p = 0.0017) [3].
• 2. Venlafaxine was baseline resolved in its enantiomers using gamma-CD or HP-beta-CD, while imp1 (Wy45494) was baseline resolved using alpha-CD [13].
• Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility [14].
• Determination of high resolution crystal structures and molecular modeling of succinic acid inhibitor complexes with IMP-1 has allowed an understanding of the potency, stereochemistry, and structure-activity relationships of these inhibitors [14].
• Previously, we have discovered that mutations G262S (yielding IMP-1) and G262A in IMP-6 stabilize the Zn(II) ligand His263 and thus the enzyme-substrate intermediate complex through a domino effect, which enhances conversion of drugs like ceftazidime, penicillins, and imipenem [15].

Physical interactions of IGF2BP1

• CRD-BP has been assigned a role in stabilizing c-myc mRNA by preventing its endonucleolytic cleavage and in repressing the translation of the leader 3 IGF-II mRNA, the major embryonic species of this message [16].

Regulatory relationships of IGF2BP1

• Thus, CRD-BP is thought to promote cell proliferation by maintaining c-Myc at critical levels [10].

Other interactions of IGF2BP1

• IMP-3 and IMP-1, two members of the IMP family with significant structural similarity, appear to have some distinct RNA targets and functions in K562 cells [17].
• The IMP-12 enzyme is quite divergent from other IMP variants: its closest relatives are IMP-8 and IMP-2 (89 and 88% sequence identity, respectively), and IMP-1 is 85% identical to IMP-12 [18].
• To our knowledge this is the first observation of a direct translational role of G3BP1 for any mRNA and the first report of a translation inhibition by IMP1 and HuD on the tau mRNA in a cell system [19].
• CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression [16].
• The coding region determinant-binding protein (CRD-BP) is an RNA binding protein that recognizes c-myc and IGF-II leader 3 mRNAs as well as the oncofetal H19 RNA [4].

Analytical, diagnostic and therapeutic context of IGF2BP1

• Log-rank testing showed that IMP-1 overexpression (p=0.0398) and an advanced clinical stage (p=0.0050) were significantly correlated with poor patient survival, whereas neither IMP-2 nor IMP-3 overexpression were associated with poor prognoses [1].
• Of these 431 strains, 357 were found by PCR to carry genes for IMP-1 type MBL (bla(IMP-1)), while only 7 and 67 strains carried the IMP-2 gene (bla(IMP-2)) and the VIM-2 gene (bla(VIM-2)), respectively [20].
• In this study, we used an electrophoretic mobility-shift assay in combination with equilibrium and kinetic analyses to characterize the assembly of the human zipcode-binding protein IMP1 on targets in the 3'-UTR from Igf-II mRNA and in H19 RNA [21].
• To analyse CRD-BP expression in human cancer tissue, paired extracts of cancer and normal colon specimens from 21 patients were analysed by immunoblotting and/or reverse transcriptase-polymerase chain reaction [22].
• In this study, 29 amino acid residue positions in and near the active-site pocket of the IMP-1 enzyme were randomized individually by site-directed mutagenesis of the corresponding codons in the bla(IMP-1) gene [23].

References