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

Ubiquitination and deubiquitination pathways play important roles in the regulation of p53 stability and activity. p53 is ubiquitinated and destabilized by E3 ubiquitin ligases and is deubiquitinated and stabilized by deubiquitinases (DUBs). We screened ovarian tumor (OTU) subfamily proteins to identify novel DUBs that stabilized p53. OTU domain-containing protein 1 (OTUD1) is a DUB belonging to the OTU family; however, its substrates and its role in cells are unknown. Here, we used an overexpression and knockdown system to show that OTUD1 is a novel regulator of p53 stability. OTUD1 overexpression increased p53 stability, whereas OTUD1 knockdown decreased p53 stability. Moreover, we observed that OTUD1 directly interacted with p53. Our results showed that OTUD1 deubiquitinated p53 and that functional OTUD1 was required for p53 stabilization. The deubiquitination activity of OTUD1 was necessary for p53 stabilization, as confirmed using an inactive OTUD1 mutant (C320S OTUD1 mutant). We also found that wild-type OTUD1 upregulated p21 and Mdm2 expression but inactive OTUD1 mutant did not. Furthermore, OTUD1 significantly suppressed colony formation. Next, we confirmed that OTUD1 overexpression increased the cleavage of caspase-3 and PARP and subsequently increased apoptosis. Together, these results suggest that OTUD1 is a novel regulator of p53 stability and activity.
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PMID:Ovarian tumor domain-containing protein 1 deubiquitinates and stabilizes p53. 2821 91

This study was performed to investigate the effects of dietary inclusion of 20% rapeseed meal (RSM) as an alternative to soybean meal (SBM) in a three-month feeding experiment with growing finishing pigs. Dietary alteration affected growth performance, several carcass traits and transcriptional responses in the skeletal muscle, but did not affect measured meat quality traits. In general, pigs fed the RSM test diet exhibited reduced growth performance compared to pigs on SBM control diet. Significant transcriptional changes in the skeletal muscle of growing pigs fed RSM diet were likely the consequence of an increased amount of fiber and higher polyunsaturated fatty acids, and presence of bioactive phytochemicals, such as glucosinolates. RNAseq pipeline using Tophat2-Cuffdiff identified 57 upregulated and 63 downregulated genes in RSM compared to SBM pigs. Significantly enriched among downregulated pathways was p53-mediated signalling involved in cellular proliferation, while activation of negative growth regulators (IER5, KLF10, BTG2, KLF11, RETREG1, PRUNE2) in RSM fed pigs provided further evidence for reduced proliferation and increased cellular death, in accordance with the observed reduction in performance traits. Upregulation of well-known metabolic controllers (PDK4, UCP3, ESRRG and ESRRB), involved in energy homeostasis (glucose and lipid metabolism, and mitochondrial function), suggested less available energy and nutrients in RSM pigs. Furthermore, several genes supported more pronounced proteolysis (ABTB1, OTUD1, PADI2, SPP1) and reduced protein synthesis (THBS1, HSF4, AP1S2) in RSM muscle tissue. In parallel, higher levels of NR4A3, PDK4 and FGF21, and a drop in adropin, ELOVL6 and CIDEC/FSP27 indicated increased lipolysis and fatty acid oxidation, reflective of lower dressing percentage. Finally, pigs exposed to RSM showed greater expression level of genes responsive to oxidative stress, indicated by upregulation of GPX1, GPX2, and TXNIP.
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PMID:Effects of long-term feeding of rapeseed meal on skeletal muscle transcriptome, production efficiency and meat quality traits in Norwegian Landrace growing-finishing pigs. 3139 Mar 56