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)

It has previously been shown that ubiquitin-specific protease 2a (USP2a) is a regulator of the Mdm2/p53 pathway. USP2a binds to Mdm2 and can deubiquitinate Mdm2 without reversing Mdm2-mediated p53 ubiquitination. Overexpression of USP2a causes accumulation of Mdm2 and promotes p53 degradation. We now show that MdmX is also a substrate for USP2a. MdmX associates with USP2a independently of Mdm2. Ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2-mediated degradation of MdmX. This correlates with the ability of wild-type USP2a to deubiquitinate MdmX. siRNA-mediated knockdown of USP2a in NTERA-2 testicular embryonal carcinoma cells and MCF7 breast cancer cells causes destabilization of MdmX and results in a decrease in MdmX protein levels, showing that endogenous USP2a participates in the regulation of MdmX stability. The therapeutic drug, cisplatin decreases MdmX protein expression. USP2a mRNA and protein levels were also reduced after cisplatin exposure. The magnitude and time course of USP2a downregulation suggests that the reduction in USP2a levels could contribute to the decrease in MdmX expression following treatment with cisplatin. Knockdown of USP2a increases the sensitivity of NTERA-2 cells to cisplatin, raising the possibility that suppression of USP2a in combination with cisplatin may be an approach for cancer therapy.
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PMID:MdmX is a substrate for the deubiquitinating enzyme USP2a. 1983 11

Previous studies have reported the miR-513b is located on the X chromosome and is preferentially expressed in testis. However, the underlying mechanisms of miR-513b involved in spermatogenesis remains unknown. In this study, we found that hsa-miR-513b-5p was highly expressed in the testes of infertile males with maturation arrest compared with normal controls. Overexpression of hsa-miR-513b-5p suppressed testicular embryonal carcinoma (NT2) cell proliferation and induced apoptosis in vitro, whereas silencing of hsa-miR-513b-5p reversed these effects. In addition, we found that interferon regulatory transcription factor 2 (IRF2) was a direct and functional target of hsa-miR-513b-5p. Silencing of endogenous IRF2 enhanced hsa-miR-513b-5p-mediated effects on cell proliferation in NT2 cells, whereas overexpression of IRF2 reversed these effects. Moreover, immunoblotting showed that overexpression of hsa-miR-513b-5p or silencing of endogenous IRF2 could promote the expression of P53. Moreover, overexpression of hsa-miR-513b-5p in the absence of p53 could also induce cell apoptosis. Together, our results suggest that hsa-miR-513b-5p suppresses NT2 cell proliferation and promotes P53 protein expression by targeting IRF2, and abnormal testicular hsa-miR-513b-5p expression may contribute to maturation arrest.
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PMID:Hsa-miR-513b-5p suppresses cell proliferation and promotes P53 expression by targeting IRF2 in testicular embryonal carcinoma cells. 2851 62

Intermediate-sized non-coding RNAs (imsncRNAs) have been shown to play important regulatory roles in the development of several eukaryotic organisms. In the present research, we selected imsncRNA 761 (imsnc761) as a research target. Expression analyses in a previous study showed that imsnc761 was down-regulated in maturation-arrested testis tissues as compared with the level in normal controls. In the present study, we found that imsnc761 could interact with DEAD-box helicase 6 (DDX6) to induce NTERA-2 (NT2 (testicular embryonal carcinoma cell)) cell apoptosis and proliferation inhibition via the p53 pathway. This interaction between imsnc761 and DDX6 also inhibited mitochondrial function and specific gene transcription and translation. To facilitate further research, we used label-free quantitation method to analyze the associated differences in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways and biological processes. This confirmed the changes in several specific pathways, which matched our molecular experimental results.
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PMID:Imsnc761 and DDX6 synergistically suppress cell proliferation and promote apoptosis via p53 in testicular embryonal carcinoma cells. 2976 12