Decreased Expression of UK114 Is Related to the Differentiation Status of Human Hepatocellular Carcinoma

Chong, Chin Liew; Huang, Shiu Feng; Hu, Cheng; Chen, Ya Ling; Chou, Hsin Ying; Chau, Gar Yang; Shew, Jin Yuh; Tsai, Yue Lin; Chen, Chiung Tong; Chang, C. Allen; Chen, Mong Liang

doi:10.1158/1055-9965.epi-07-0506

Cited by 10 publications

(7 citation statements)

References 37 publications

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“…It has been reported that protein expression levels are remarkably reduced in hepatocellular tumors compared with normal liver tissues. This result gave rise to the suggestion that ribonuclease UK114 may be an important biomarker for hepatic carcinoma [49]. Therefore, our current observation demonstrates that the reduced expression of ribonuclease UK114 in RCC raises the possibility of its association and correlation with the pathologic status and carcinogenesis of RCC formation..…”

Section: Rcc-associated Proteinssupporting

confidence: 71%

Quantitative Proteomics Analysis of Differentially Expressed Proteins Involved in Renal Clear Cell Carcinoma by Shotgun Approach Coupled with Stable Isotope Dimethyl Labeling

Liang¹,

Kuo²,

Chi

et al. 2014

J Proteomics Bioinform

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Section: Rcc-associated Proteinssupporting

confidence: 71%

Quantitative Proteomics Analysis of Differentially Expressed Proteins Involved in Renal Clear Cell Carcinoma by Shotgun Approach Coupled with Stable Isotope Dimethyl Labeling

Liang¹,

Kuo²,

Chi

et al. 2014

J Proteomics Bioinform

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“…In Saccharomyces cerevisiae, the SHM1 isozyme of SHMT and the yeast RidA homolog (Yil051cp) both localize to the mitochondria (32,33). In some mammalian cell lines, RidA-like UK114 is produced in the cytoplasm (34), while SHMT isozymes are found in both the cytosol and mitochondria (35). Developing a better understanding of the link between RidA homologs and SHMT may lead to better chemotherapeutics to combat diseases such as cancer, as tumor cells rely heavily on flux through SHMT to meet the rampant demand for glycine and one-carbon units necessary for rapid cell growth and division (36)(37)(38).…”

Section: Resultsmentioning

confidence: 99%

2-Aminoacrylate Stress Induces a Context-Dependent Glycine Requirement in ridA Strains of Salmonella enterica

Ernst

Downs

2016

J Bacteriol

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The reactive enamine 2-aminoacrylate (2AA) is a metabolic stressor capable of damaging cellular components. Members of the broadly conserved Rid (RidA/YER057c/UK114) protein family mitigate 2AA stress in vivo by facilitating enamine and/or imine hydrolysis. Previous work showed that 2AA accumulation in ridA strains of Salmonella enterica led to the inactivation of multiple target enzymes, including serine hydroxymethyltransferase (GlyA). However, the specific cause of a ridA strain's inability to grow during periods of 2AA stress had yet to be determined. Work presented here shows that glycine supplementation suppressed all 2AA-dependent ridA strain growth defects described to date. Depending on the metabolic context, glycine appeared to suppress ridA strain growth defects by eliciting a GcvB small RNA-dependent regulatory response or by serving as a precursor to one-carbon units produced by the glycine cleavage complex (GCV). In either case, the data suggest that GlyA is the most physiologically sensitive target of 2AA inactivation in S. enterica. The universally conserved nature of GlyA among free-living organisms highlights the importance of RidA in mitigating 2AA stress. IMPORTANCEThe RidA stress response prevents 2-aminoacrylate (2AA) damage from occurring in prokaryotes and eukaryotes alike. 2AA inactivation of serine hydroxymethyltransferase (GlyA) from Salmonella enterica restricts glycine and one-carbon production, ultimately reducing fitness of the organism. The cooccurrence of genes encoding 2AA production enzymes and serine hydroxymethyltransferase (SHMT) in many genomes may in part underlie the evolutionary selection for Rid proteins to maintain appropriate glycine and one-carbon metabolism throughout life. R id (RidA/YER057c/UK114) proteins are found throughout each kingdom of life, indicating that these proteins play fundamental roles in cellular processes. Bioinformatics analyses identified eight subgroups within the Rid protein family (1). The archetypal RidA subfamily is broadly distributed and includes the best-studied RidA enzyme from Salmonella enterica, while the remaining seven Rid subgroups are primarily restricted to bacteria. In S. enterica, RidA is known to preempt metabolic damage caused by the unbound reactive enamine 2-aminoacrylate (2AA) (2). In the absence of RidA, 2AA persisted in solution long enough to inactivate multiple target enzymes in vivo and in vitro (2-4). RidA proteins isolated from organisms spanning the tree of life displayed similar enamine and imine deaminase activities (5, 6), suggesting that RidA enzymes have a conserved role in preventing 2AA stress.2AA stress arises as a consequence of some pyridoxal 5=-phosphate (PLP)-dependent enzyme activities. Previous analysis of S. enterica showed that PLP-dependent serine/threonine dehydratases (IlvA/TdcB; EC 4.3.1.19), cysteine desulfhydrase (CdsH; EC 4.4.1.1), and diaminopropionate ammonia-lyase (DpaL; EC 4.3.1.15) generated free 2AA from exogenous serine, cysteine, and diaminopropionate, respectively, leading ...

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“…The expression of ribonuclease UK114, a translational inhibitor mostly present in the liver and kidney, was 2.2-fold lower in the PLP group, meeting the requirement for protein synthesis for liver regeneration. In a clinical study, downregulation of ribonuclease UK114 was observed in human hepatocellular carcinoma [38]. …”

Section: Discussionmentioning

confidence: 99%

Protective effect of Phellinus linteus polysaccharide extracts against thioacetamide-induced liver fibrosis in rats: a proteomics analysis

Wang

Park

et al. 2012

Chinese Medicine

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BackgroundThe hepatoprotective potential of Phellinus linteus polysaccharide (PLP) extracts has been described. However, the molecular mechanism of PLP for the inhibition of liver fibrosis is unclear. This study aims to investigate the molecular protein signatures involved in the hepatoprotective mechanisms of PLP via a proteomics approach using a thioacetamide (TAA)-induced liver fibrosis rat model.MethodsMale Sprague–Dawley rats were divided into three groups of six as follows: Normal group; TAA group, in which rats received TAA only; and PLP group, in which rats received PLP and TAA. Liver fibrosis was induced in the rats by repeated intraperitoneal injections of TAA at a dose of 200 mg/kg body weight twice a week for 4 weeks. PLP was given orally at a dose of 50 mg/kg body weight twice a day from the beginning of the TAA treatment until the end of the experiment. The development of liver cirrhosis was verified by histological examination. Liver proteomes were established by two-dimensional gel electrophoresis. Proteins with significantly altered expression levels were identified by matrix-assisted laser desorption/ionization-time of flight/time of flight mass spectrometry and the differentially expressed proteins were validated by immunohistochemical staining and reverse transcription polymerase chain reaction.ResultsHistological staining showed a remarkable reduction in liver fibrosis in the rats with PLP treatment. A total of 13 differentially expressed proteins including actin, tubulin alpha-1C chain, preprohaptoglobin, hemopexin, galectin-5, glutathione S-transferase alpha-4 (GSTA4), branched chain keto acid dehydrogenase hterotetrameric E1 subunit alpha (BCKDHA), glutathione S-transferase mu (GSTmu); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); thiosulfate sulfurtransferase (TFT); betaine-homocysteine S-methyltransferase 1 (BHMT1); quinoid dihydropteridine reductase (QDPR); ribonuclease UK114 were observed between the TAA and PLP groups. These proteins are involved in oxidative stress, heme and iron metabolism, cysteine metabolism, and branched-chain amino acid catabolism.ConclusionThe proteomics data indicate that P. linteus may be protective against TAA-induced liver fibrosis via regulation of oxidative stress pathways, heat shock pathways, and metabolic pathways for amino acids and nucleic acids.

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Decreased Expression of UK114 Is Related to the Differentiation Status of Human Hepatocellular Carcinoma

Cited by 10 publications

References 37 publications

Quantitative Proteomics Analysis of Differentially Expressed Proteins Involved in Renal Clear Cell Carcinoma by Shotgun Approach Coupled with Stable Isotope Dimethyl Labeling

Quantitative Proteomics Analysis of Differentially Expressed Proteins Involved in Renal Clear Cell Carcinoma by Shotgun Approach Coupled with Stable Isotope Dimethyl Labeling

2-Aminoacrylate Stress Induces a Context-Dependent Glycine Requirement in ridA Strains of Salmonella enterica

Protective effect of Phellinus linteus polysaccharide extracts against thioacetamide-induced liver fibrosis in rats: a proteomics analysis

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