Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deletion at chromosome 3p21.3 is the earliest and the most frequently observed genetic alteration in lung cancer, suggesting that the region contains tumor suppressor gene(s) (TSG). Identification of those genes may lead to the development both of biomarkers to identify high-risk individuals and novel therapeutics. Previously, we cloned the H37/Luca15/RBM5 gene from 3p21.3 and showed its TSG characteristics. To investigate the physiologic function of H37 in the lung and its mechanism of tumor suppression, we have stably transfected H37 into A549 non-small cell lung cancer cells. A549/H37 cells show significant growth inhibition compared with the vector controls by in vitro and in vivo cell proliferation assays. Using this lung cancer cell model, we have found that the molecular mechanism of H37 tumor suppression involves both cell cycle (G(1)) arrest and apoptosis. To further define H37's function in cell cycle/apoptotic pathways, we investigated differential expression profiles of various cell cycle and apoptosis regulatory proteins using Western blot analysis. Both cyclin A and phophorylated RB levels were decreased in H37-transfected cells, whereas expression of Bax protein was increased. Mitochondrial regulation of apoptosis further downstream of Bax was investigated, showing change in the mitochondrial membrane potential, cytochrome c release into the cytosol, and enhanced caspase-9 and caspase-3 activities. We also report that H37 may mediate apoptosis in a p53-independent manner, and Bax knockdown by small interfering RNA suggests Bax plays a functional role downstream of H37. Lastly, we proposed a tumor suppression model of H37 as a post-transcriptional regulator for cell cycle/apoptotic-related proteins.
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PMID:3p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis. 1658 63

RBM5 (RNA-binding motif protein 5), a nuclear RNA binding protein, is known to trigger apoptosis and induce cell cycle arrest by regulating the activity of the tumor suppressor protein p53. However, its expression and function in spinal cord injury (SCI) are still unknown. To investigate whether RBM5 is involved in central nervous system injury and repair, we performed an acute SCI model in adult rats in this study. Our results showed RBM5 was unregulated significantly after SCI, which was accompanied with an increase in the levels of apoptotic proteins such as p53, Bax, and active caspase-3. Immunofluorescent labeling also showed that traumatic SCI induced RBM5 location changes and co-localization with active caspase-3 in neurons. To further probe the role of RBM5, a neuronal cell line PC12 was employed to establish an apoptotic model. Knockdown of RBM5 apparently decreased the level of p53 as well as active caspase-3, demonstrating its pro-apoptotic role in neurons by regulating expressions of p53 and caspase-3. Taken together, our findings indicate that RBM5 promotes neuronal apoptosis through modulating p53 signaling pathway following SCI.
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PMID:RBM5 and p53 expression after rat spinal cord injury: implications for neuronal apoptosis. 2557 65

RBM5 has been reported to be a candidate tumor suppressor gene which plays an important role in the induction of apoptosis. In this study, we investigated the effect of miR-483-5p on apoptosis of lung cancer cells and the underlying mechanism. We found that the expression of miR-483-5p mRNA was significantly up-regulated in lung cancer compared with adjacent para-cancerous tissues by using real-time PCR. Silencing miR-483-5p promoted A549 cell apoptosis and enhanced caspase-3 activity by flow cytometry with annexin V-FITC/PI staining and caspase-3 activity report kit. Western blotting demonstrated that miR-483-5p mimicked down-regulated RBM5 protein expression and miR-483-5p inhibitor up-regulated RBM5 protein expression. With additional bioinformatics analysis, we confirmed that RBM5 is a target gene of miR-483-5p and is favored for treating NSCLC. The immunohistochemical pattern of RBM5 could be used to predictoutcome for NSCLC. In conclusion, our results support that RBM5 expression can be regulated by miR-483-5p which is a prognostic marker for NSCLC patients. miR-483-5p inhibitor plays a role in lung cancer through targeting RBM5 to induce apoptosis.
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PMID:Effect of miR-483-5p on apoptosis of lung cancer cells through targeting of RBM5. 3193 44