PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expr...PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.展开更多
Background Activation of c-Jun NH2-terminal kinase （JNK） has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury （TBI）. However, the underlying mo...Background Activation of c-Jun NH2-terminal kinase （JNK） has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury （TBI）. However, the underlying molecular pathway remains unclear. Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI. Methods A total of 186 male Sprague-Dawley （SD） rats （300-350 g） were used in this study. By randomized block method rats were randomly divided into four groups： sham-operated （n=46）, TBI （n=60）, TBI ＋ dimethyl sulfoxide （DMSO） （n=40）, and TBI ＋ SP600125 （n=40）. JNK was treated with SP600125, a specific JNK inhibitor. JNK, p-P53, Beclin-1, damage-regulated autophagy modulator （DRAM） and p-bcl-2 were evaluated by Western blotting analysis. The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry, and the expression of Beclin-l-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation. Multiple-group comparisons were conducted using analysis of variance （ANOVA）. P values of less than 0.05 were considered statistically significant. Results It was observed that the expression of JNK, p-P53, Beclin-1, DRAM and p-bcl-2 was increasing after TBI, and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons. But these were significantly inhibited in SP600125 group compared with sham group and TBI＋SP600125 group （P 〈0.05）. The expression of Beclin-l-Bcl-2/Bcl-xL complexes was reduced after TBI. Conclusion JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.展开更多
Evasion of apoptosis is one of the hallmarks of hepatocellular carcinoma(HCC)that results in treatment resistance.Recently,autophagy was reported to induce cell death in HCC,highlighting the tumorsuppressing effects o...Evasion of apoptosis is one of the hallmarks of hepatocellular carcinoma(HCC)that results in treatment resistance.Recently,autophagy was reported to induce cell death in HCC,highlighting the tumorsuppressing effects of autophagy on HCC.This review summarizes our current understanding of the HCC-suppressing effects of macroautophagy(hereafter referred to as autophagy)to provide insights into the molecular mechanisms that may be essential for the development of autophagy-targeting therapeutic strategies for HCC.展开更多
基金support by the Ministerio Educación y CienciaMinisterio de Economía y Competitividad of Spain(until June 2013)
文摘PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.
基金This work was supported by a grant from Hebei Province Natural Science Foundation （No. C2009001247）. The authors declare that there are no conflicts of interest.Acknowledgments： We thank Dr. CUI Jian-zhong and Dr. GAO Jun-ling for their help and generous gift of antibodies for Western blotting.
文摘Background Activation of c-Jun NH2-terminal kinase （JNK） has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury （TBI）. However, the underlying molecular pathway remains unclear. Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI. Methods A total of 186 male Sprague-Dawley （SD） rats （300-350 g） were used in this study. By randomized block method rats were randomly divided into four groups： sham-operated （n=46）, TBI （n=60）, TBI ＋ dimethyl sulfoxide （DMSO） （n=40）, and TBI ＋ SP600125 （n=40）. JNK was treated with SP600125, a specific JNK inhibitor. JNK, p-P53, Beclin-1, damage-regulated autophagy modulator （DRAM） and p-bcl-2 were evaluated by Western blotting analysis. The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry, and the expression of Beclin-l-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation. Multiple-group comparisons were conducted using analysis of variance （ANOVA）. P values of less than 0.05 were considered statistically significant. Results It was observed that the expression of JNK, p-P53, Beclin-1, DRAM and p-bcl-2 was increasing after TBI, and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons. But these were significantly inhibited in SP600125 group compared with sham group and TBI＋SP600125 group （P 〈0.05）. The expression of Beclin-l-Bcl-2/Bcl-xL complexes was reduced after TBI. Conclusion JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.
基金This work was supported by National Natural Science Foundation of China(81402556,81773168)the Foundation of Beijing Institute of Hepatology(BJIH-01715,2018-1-1).
文摘Evasion of apoptosis is one of the hallmarks of hepatocellular carcinoma(HCC)that results in treatment resistance.Recently,autophagy was reported to induce cell death in HCC,highlighting the tumorsuppressing effects of autophagy on HCC.This review summarizes our current understanding of the HCC-suppressing effects of macroautophagy(hereafter referred to as autophagy)to provide insights into the molecular mechanisms that may be essential for the development of autophagy-targeting therapeutic strategies for HCC.
