Disease relevance of CIRBP

• However, cells depleted of mitochondria were still able to upregulate RBM3 and CIRP in response to hypoxia [1].
• Sixty-seven sequences met the criteria for increased expression (including cold-inducible genes CIRBP and RNA binding motif 3), and 100 sequences showed decreased expression as a result of hypothermia [2].
• Analysis of Cirp expression in the testes will help elucidate the molecular mechanisms leading to male infertility [3].
• To elucidate the role played by Cirp in spermatogenesis, we investigated its expression levels during spermatogenesis and after heat stress [3].
• In human testis with varicocele analyzed immunohistochemically, germ cells expressed less Cirp protein than those in the testis without varicocele [3].

High impact information on CIRBP

• Immunofluorescence microscopy showed that CIRP was localized in the nucleoplasm of BALB/3T3 mouse fibroblasts [4].
• Northwestern analyses indicate that A18 hnRNP binds specifically to the 3'-untranslated region of RPA2 transcript independently of its poly(A) tail, whereas the poly(A) tail of thioredoxin mRNA reinforces binding [5].
• Moreover, cell lines expressing reduced levels of A18 hnRNP are more sensitive to UV radiation [5].
• These data suggest that A18 hnRNP plays a protective role against genotoxic stresses by translocating to the cytosol and stabilizing specific transcripts involved in cell survival [5].
• Rbm3 may play important roles distinct from those played by Cirp in spermatogenesis and cryptorchidism by regulating the gene expression in Sertoli cells [6].

Biological context of CIRBP

• Hypoxia-induced RBM3 or CIRP transcription was inhibited by the respiratory chain inhibitors NaN(3) and cyanide in a dose-dependent fashion [1].
• Hypoxia also induced upregulation of RBM3 and CIRP in the murine HIF-1beta-deficient cell line, Hepa-1 c4 [1].
• Thus the putative A18 hnRNP is the first hnRNP whose mRNA is specifically regulated in response to UV-induced DNA damage; accordingly, it may play some role in repair of UV-type DNA damage [7].
• Combined with the different tissue distribution of expression, these results suggest that RBM3 and CIRP play distinct roles in cold responses of human cells [8].
• In NC65 cells, the kinetics of RBM3 induction was different from that of CIRP [8].

Anatomical context of CIRBP

• These results indicate that CIRP plays an essential role in cold-induced growth suppression of mouse fibroblasts [4].
• These results demonstrated that CIRP expression is down-regulated at elevated temperature in male germ cells of mice and humans [3].
• Also, a high level of Cirp protein was detected immunohistochemically in the nucleus of primary spermatocytes [3].
• These results suggest that CIRP may participate in the cell cycle regulation of normal endometrium and the loss of its expression may be involved in endometrial carcinogenesis [9].
• CIRP was localized in the nuclei of glandular, stromal, and endothelial cells [9].

Associations of CIRBP with chemical compounds

• We found that an arginine- and glycine-rich region of xCIRP2, termed the RG4 domain, was a target of xPRMT1 for methylation in vitro. xCIRP2 expressed in cultured cells accumulated in the nucleus as does mammalian CIRP [10].

Regulatory relationships of CIRBP

• Thus, RBM3 and CIRP are adaptatively expressed in response to hypoxia by a mechanism that involves neither HIF-1 nor mitochondria [1].

Other interactions of CIRBP

• In contrast, iron chelators induced VEGF but not RBM3 or CIRP [1].
• Recently, CIRP, a member of the glycine-rich RNA-binding protein (GRP) family, has been identified as the first cold-shock protein in mammalian cells [8].

Analytical, diagnostic and therapeutic context of CIRBP

• RNA was extracted, and the hypothermic response was confirmed by examining the expression of the cold-induced RNA-binding protein (CIRBP) gene by RT-PCR [2].
• The human CIRP gene has been mapped to the chromosomal locus 19p13.3 by fluorescence in-situ hybridization [11].
• We investigated the immunohistochemical expression of CIRP in 39 endometrial carcinomas, 12 endometrial hyperplasias, and 27 normal endometria using polyclonal antibody against CIRP and confirmed by Western blot analysis [9].
• Northern blot analysis revealed that the CIRP transcripts were ubiquitously expressed in various tissues [12].
• In the hippocampus of postischemic rats, CIRP mRNA level decreased from 3-6 h after the onset of reperfusion, while it did not change in the cerebral cortex [12].

References