Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure.
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PMID:A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases. 2365 77

The transcription factor E2F is the principal target of the tumor suppressor pRB. E2F plays crucial roles not only in cell proliferation by activating growth-related genes but also in tumor suppression by activating pro-apoptotic and growth-suppressive genes. We previously reported that, in human normal fibroblasts, the tumor suppressor genes ARF, p27(Kip1) and TAp73 are activated by deregulated E2F activity induced by forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. In contrast, growth-related E2F targets are activated by both E2F activities, underscoring the roles of deregulated E2F in tumor suppression in the context of dysfunctional pRB. In this study, to further understand the roles of deregulated E2F, we explored new targets that are specifically activated by deregulated E2F using DNA microarray. The analysis identified nine novel targets (BIM, RASSF1, PPP1R13B, JMY, MOAP1, RBM38, ABTB1, RBBP4 and RBBP7), many of which are involved in the p53 and RB tumor suppressor pathways. Among these genes, the BIM gene was shown to be activated via atypical E2F-responsive promoter elements and to contribute to E2F1-mediated apoptosis. Our results underscore crucial roles of deregulated E2F in growth suppression to counteract loss of pRB function.
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PMID:Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts. 2620 19

Silicosis is a progressive fibrotic disease of lung tissue caused by long-term inhalation of SiO2. However, relatively few studies of the direct effects of SiO2 on lung fibroblasts have been performed. PPP1R13B is a major member of the apoptosis-stimulating proteins of the p53 family, but its role in pulmonary fibrosis is unclear. To elucidate the role of PPP1R13B in the pathological process of silicosis, we explored the molecular mechanisms related to PPP1R13B and the functional effects of proliferation and migration of fibroblasts. Through lentivirus transfection, Western blotting, and fluorescent in situ hybridization experiments, we found that SiO2 downregulated circRNA-012091 (circ-012091) expression in lung fibroblasts and induced upregulation of downstream PPP1R13B. Transfection of L929 cells with PPP1R13B CRISPR NIC plasmid inhibited the upregulation of endoplasmic reticulum stress (ERS) and autophagy-related protein expression in lung fibroblasts treated with SiO2, and induced decreases in cell proliferation, migration, and viability. Transfection of L929 cells with the PPP1R13B CRISPR ACT plasmid induced increases in cell proliferation, migration, and viability. In addition, the ERS inhibitor salubrinal and the autophagy inhibitor 3-methyladenine inhibited the increased migration of L929 cells transfected with the PPP1R13B CRISPR ACT plasmid. These results suggest that PPP1R13B regulated by circ-012091 promotes the proliferation and migration of lung fibroblasts through ERS and autophagy, and plays a crucial role in the development of pulmonary fibrosis in silicosis.
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PMID:CircRNA-012091/PPP1R13B-mediated Lung Fibrotic Response in Silicosis via Endoplasmic Reticulum Stress and Autophagy. 3090 29