Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)hav...Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.展开更多
PDI is a molecular chaperone and plays an important role in Endoplasmic Reticulum quality control (ERQC).PDI participates in the refolding of the misfolded/unfolded proteins to maintain cellular homeostasis under diff...PDI is a molecular chaperone and plays an important role in Endoplasmic Reticulum quality control (ERQC).PDI participates in the refolding of the misfolded/unfolded proteins to maintain cellular homeostasis under differentstresses. However, bioinformatic characteristics and potential functions of PDIs in diatom Phaeodactylumtricornutum (Pt) are still unknown so far. Hence, the genome-wide characteristics of PtPDI proteins in P. tricornutumwere first studied via bioinformatic and transcriptomic methods. 42 PtPDI genes were identified from thegenome of P. tricornutum. The motif, protein structure, classification, number of introns, phylogenetic relationship,and the expression level of 42 PtPDI genes under the tunicamycin stress were analyzed. A pair of tandemduplicated genes (PtPDI15 and PtPDI18) was observed in P. tricornutum. The 42 PtPDIs with different genecharacteristics were divided into three independent clades, indicating different evolutional relationships and functionsof these PtPDIs. The 14 up-regulated PtPDI genes under the tunicamycin treatment might have a positiveeffect on the ER quality control of the unfolded/misfolded proteins, while the 7 down-regulated PtPDIs mightnegatively affect the ERQC. The characteristics of all 42 PtPDIs and their proposed working model here providea comprehensive understanding of the PtPDIs gene family. The differential expression of 21 PtPDIs will be usefulfor further functional study in the ERQC.展开更多
pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical p...pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical properties, hydrophilicity/hydrophobicity, signal peptide, secondary structure, coiled coil, transmembrane domains, O-glycogylation site, active site, subcellular localization, functional structural domains and three-dimensional structure were analyzed by a series of bioinformatics software. The results showed that mPDI was a hydrophobic and stable protein with 3 coiled coils, 30-glycogylation sites, 2 structural domains of thioredoxin, 2 active sites of thioredoxin, and located in rough endoplasmic reticulum. It has 512 amino acids, the theoretical pl is 4.98, and signal peptide located in 1-24AA. In the secondary structure, a-helix, random coil, extended chain is 26.37%, 53.32%, 20.31% respectively. The validation of modeling accords with the stereochemistry.展开更多
Spinal cord ischemia/reperfusion injury is a stress injury to the spinal cord. Our previous studies using differential proteomics identified 21 differentially expressed proteins （n 〉 2） in rabbits with spinal cord ...Spinal cord ischemia/reperfusion injury is a stress injury to the spinal cord. Our previous studies using differential proteomics identified 21 differentially expressed proteins （n 〉 2） in rabbits with spinal cord ischemia/reperfusion injury. Of these proteins, stress-related proteins included protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70. In this study, we established New Zealand rabbit models of spinal cord ischemia/reperfusion injury by abdominal aorta occlusion. Results demonstrated that hind limb function initially improved after spinal cord ischemia/reperfusion injury, but then deteriorated. The pathological morphology of the spinal cord became aggravated, but lessened 24 hours after reperfusion. However, the numbers of motor neurons and interneurons in the spinal cord gradually decreased. The expression of protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70 was induced by ischemia/reperfusion injury. The expression of these proteins increased within 12 hours after reperfusion, and then decreased, reached a minimum at 24 hours, but subsequently increased again to similar levels seen at 6-12 hours, showing a characterization of induction-inhibition-induc- tion. These three proteins were expressed only in cytoplasm but not in the nuclei. Moreover, the expression was higher in interneurons than in motor neurons, and the survival rate of interneurons was greater than that of motor neurons. It is assumed that the expression of stress-related proteins exhibited a protective effect on neurons.展开更多
Objective Protein disulfide isomerase A2(PDIA2),a member of the protein disulfide isomerase family,plays a key role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds,together w...Objective Protein disulfide isomerase A2(PDIA2),a member of the protein disulfide isomerase family,plays a key role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds,together with enzymes such as thiol isomerase,oxidase,and reductase.This study investigated the clinical significance and potential functions of PDIA2 in glioma.Methods The expression of PDIA2 in gliomas was explored using The Cancer Genome Atlas and Gene Expression Omnibus databases.We analyzed the clinical characteristics of glioma patients and the prognostic and diagnostic value of PDIA2 expression.Kaplan-Meier and Cox regression analyses were used to examine the effect of PDIA2 expression on overall survival,progression-free interval,and disease-specific survival.Furthermore,we performed Gene Set Enrichment Analysis and immune infiltration analysis to investigate the functions of PDIA2.PDIA2 mRNA and protein expression was evaluated in cell lines and glioma tissues.Results PDIA2 was expressed at low levels in glioma patients.Kaplan-Meier survival analysis showed that glioma patients with low PDIA2 levels had a worse prognosis than those with high PDIA2 levels.Receiver operating characteristic curve analysis indicated the diagnostic and prognostic ability of PDIA2(area under the curve=0.918).Pathways associated with PD1,PI3K/AKT,cancer immunotherapy via PD1 blockade,Fceri-mediated NF-kB activation,FOXM1,and DNA repair were enriched in glioma patients with low levels of PDIA2.PDIA2 expression levels were negatively correlated with immune cell infiltrate levels.Conclusion PDIA2 levels are significantly downregulated in glioma.PDIA2 expression may be a potential biomarker for the diagnosis and prognosis of glioma patients.展开更多
Newly synthesized membrane and secretory proteins in cells undergo folding in the endoplasmic reticulum with the introduction of disulfide bonds and acquire the correct three-dimensional structure. Disulfide bonds are...Newly synthesized membrane and secretory proteins in cells undergo folding in the endoplasmic reticulum with the introduction of disulfide bonds and acquire the correct three-dimensional structure. Disulfide bonds are especially important for protein folding. It has been thought that formation of protein disulfide bonds in eukaryotes is mainly carried out by an enzyme called protein disulfide isomerase. Proteins, bearing the C-terminus of amino acids sequences with His-Asp-Glu-Leu (HDEL) sequence in yeast, in the endoplasmic reticulum (ER), which is a eukaryotic cellular organelle involved in protein synthesis, processing, and transport, have been considered to recycle between ER and Golgi apparatus. The proposal for this recycling model derives from the study of an HDEL-tagged fusion protein. Here, the localization and oligosaccharide modification of protein disulfide isomerase were investigated in yeast, and showed the first direct evidence that this intrinsic ER protein transports from ER to Golgi. Results suggest that this native protein is also accessible to post-ER enzymes, and yet accumulates in the ER.展开更多
Rice blast,caused by Magnaporthe oryzae,is a fungal disease that causes devastating damage to rice production worldwide.During infection,pathogens secrete effector proteins that modulate plant immunity.Disulfide bond ...Rice blast,caused by Magnaporthe oryzae,is a fungal disease that causes devastating damage to rice production worldwide.During infection,pathogens secrete effector proteins that modulate plant immunity.Disulfide bond formation catalyzed by protein disulfide isomerases(PDI)is essential for protein folding and maturation.However,the biological function of Pdi1 in M.oryzae has not yet been characterized.In this study,we identified the endoplasmic reticulum(ER)-located protein,MoPdi1,in M.oryzae.MoPdi1 regulates conidiation,cell wall stress,and pathogenicity of M.oryzae.Furthermore,the CGHC active sites in the a and a'redox domain of MoPdi1 were essential for the biological function of MoPDI1.Further tests demonstrated that MoPdi1 was involved in the regulation of ER stress and positively regulated ER phagy.We also found that MoPdi1 interacted with MoHut1.Deletion of MoPDI1 led to the bereft of MoHut1 dimerization,which depends on the formation of disulfide bonds.In addition,MoPdi1 affected the normal secretion of the cytoplasmic effector AVR-Pia.We provided evidence that MoHut1 is important for the vegetative growth,conidiation,and pathogenicity in M.oryzae.Therefore,our findings could provide a suitable target point for designing antifungal agrochemicals against rice blast fungus.展开更多
Disulfide bond formation protein A （DsbA） is one of the important helper proteins for folding in protein synthesis in vivo. In this study, purification of recombinant DsbA was investigated by examining four importan...Disulfide bond formation protein A （DsbA） is one of the important helper proteins for folding in protein synthesis in vivo. In this study, purification of recombinant DsbA was investigated by examining four important factors with Box-Behnken design method, a statistic-based design of experiments. The optimal operation conditions were obtained by adopting the effectiveness coefficient method on the multi-objective problem, which takes the protein recovery, purification efficiency and throughput of ion-exchange chromatography into account. After the optimization, protein recovery of 96.8% and purity higher than 95% DsbA was achieved, and the productivity was （377.9±1.7） mg soluble DsbA per liter broth. The purified protein was identified by peptide mass fingerprinting matching the record of gil2624856, a mutant of DsbA. The DsbA was preliminarily applied to the refolding of denatured lysozyme in vitro.展开更多
Correct folding of nascent peptides occurs in the endoplasmic reticulum(ER).It is a complicate process primarily accomplished by the coordination of multiple redox proteins including members of the protein disulfide i...Correct folding of nascent peptides occurs in the endoplasmic reticulum(ER).It is a complicate process primarily accomplished by the coordination of multiple redox proteins including members of the protein disulfide isomerase(PDI)family.As a critical member of the PDI family,thioredoxin domain containing protein 5(TXNDC5)assists the folding of newly synthesized peptides to their mature form through series of disulfide bond exchange reactions.Interestingly,TXNDC5 is frequently found overexpressed in specimens of many human diseases including various types of cancer.In this review,we summarized the biochemical function of TXNDC5 in mammalian cells and the recent progress on the understanding of its role and molecular mechanisms in cancer development.Findings of TXNDC5 in the activation of intracellular signaling pathways,stimulation of cell growth&proliferation,facilitation of cell survival and modulation of extracellular matrix to affect cancer cell invasion and metastasis are reviewed.These published studies suggest that strategies of targeting TXNDC5 can be developed as potentially valuable methods for the treatment of certain types of cancer in patients.展开更多
Protein disulfide isomerases （PDIs） are known to play important roles in the folding of nascent proteins and in the formation of disulfide bonds. Recently, we identified a PDI from Chlamydomonas reinhardtii （CrPDI2...Protein disulfide isomerases （PDIs） are known to play important roles in the folding of nascent proteins and in the formation of disulfide bonds. Recently, we identified a PDI from Chlamydomonas reinhardtii （CrPDI2） by a mass spectrometry approach that is specifically enriched by heparin affinity chromatography in samples taken during the night phase. Here, we show that the recombinant CrPDI2 is a redox-active protein. It is reduced by thioredoxin reductase and catalyzes itself the reduction of insulin chains and the oxidative refolding of scrambled RNase A. By immunoblots, we confirm a high-amplitude change in abundance of the heparin-bound CrPDI2 during subjective night. Interestingly, we find that CrPDI2 is present in protein complexes of different sizes at both day and night. Among three identified interac- tion partners, one （a 2-cys peroxiredoxin） is present only during the night phase. To study a potential function of CrPDI2 within the circadian system, we have overexpressed its gene. Two transgenic lines were used to measure the rhythm of phototaxis~ In the transgenic strains, a change in the acrophase was observed. This indicates that CrPDI2 is involved in the circadian signaling pathway and, together with the night phase-specific interaction of CrPDI2 and a peroxiredoxin, these findings suggest a close coupling of redox processes and the circadian clock in C. reinhardtii.展开更多
文摘Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.
基金the funding of Educational and Scientific Research Projects for Young and Middle-Aged Teachers in Fujian Province(Grant Number:2022JAT220693)Natural Science Foundation of Guangdong Province(Grant Number:2022A1515012141)+2 种基金the Program for University Innovation Team of Guangdong Province(Grant Number:2022KCXTD008)National Natural Science Foundation of China(92158201 and 42376001)the Innovation and Entrepreneurship Project of Shantou(201112176541391).
文摘PDI is a molecular chaperone and plays an important role in Endoplasmic Reticulum quality control (ERQC).PDI participates in the refolding of the misfolded/unfolded proteins to maintain cellular homeostasis under differentstresses. However, bioinformatic characteristics and potential functions of PDIs in diatom Phaeodactylumtricornutum (Pt) are still unknown so far. Hence, the genome-wide characteristics of PtPDI proteins in P. tricornutumwere first studied via bioinformatic and transcriptomic methods. 42 PtPDI genes were identified from thegenome of P. tricornutum. The motif, protein structure, classification, number of introns, phylogenetic relationship,and the expression level of 42 PtPDI genes under the tunicamycin stress were analyzed. A pair of tandemduplicated genes (PtPDI15 and PtPDI18) was observed in P. tricornutum. The 42 PtPDIs with different genecharacteristics were divided into three independent clades, indicating different evolutional relationships and functionsof these PtPDIs. The 14 up-regulated PtPDI genes under the tunicamycin treatment might have a positiveeffect on the ER quality control of the unfolded/misfolded proteins, while the 7 down-regulated PtPDIs mightnegatively affect the ERQC. The characteristics of all 42 PtPDIs and their proposed working model here providea comprehensive understanding of the PtPDIs gene family. The differential expression of 21 PtPDIs will be usefulfor further functional study in the ERQC.
文摘pdi gene from Medicago sativa L. ,encoding Protein Disulfide Isomerase（ mPDI ）, has been cloned and sequenced. According to the mRNA and amino acid sequence, the character of mPDI such as the physical and chemical properties, hydrophilicity/hydrophobicity, signal peptide, secondary structure, coiled coil, transmembrane domains, O-glycogylation site, active site, subcellular localization, functional structural domains and three-dimensional structure were analyzed by a series of bioinformatics software. The results showed that mPDI was a hydrophobic and stable protein with 3 coiled coils, 30-glycogylation sites, 2 structural domains of thioredoxin, 2 active sites of thioredoxin, and located in rough endoplasmic reticulum. It has 512 amino acids, the theoretical pl is 4.98, and signal peptide located in 1-24AA. In the secondary structure, a-helix, random coil, extended chain is 26.37%, 53.32%, 20.31% respectively. The validation of modeling accords with the stereochemistry.
基金supported by the National Natural Science Foundation of China, No. 30872609
文摘Spinal cord ischemia/reperfusion injury is a stress injury to the spinal cord. Our previous studies using differential proteomics identified 21 differentially expressed proteins （n 〉 2） in rabbits with spinal cord ischemia/reperfusion injury. Of these proteins, stress-related proteins included protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70. In this study, we established New Zealand rabbit models of spinal cord ischemia/reperfusion injury by abdominal aorta occlusion. Results demonstrated that hind limb function initially improved after spinal cord ischemia/reperfusion injury, but then deteriorated. The pathological morphology of the spinal cord became aggravated, but lessened 24 hours after reperfusion. However, the numbers of motor neurons and interneurons in the spinal cord gradually decreased. The expression of protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70 was induced by ischemia/reperfusion injury. The expression of these proteins increased within 12 hours after reperfusion, and then decreased, reached a minimum at 24 hours, but subsequently increased again to similar levels seen at 6-12 hours, showing a characterization of induction-inhibition-induc- tion. These three proteins were expressed only in cytoplasm but not in the nuclei. Moreover, the expression was higher in interneurons than in motor neurons, and the survival rate of interneurons was greater than that of motor neurons. It is assumed that the expression of stress-related proteins exhibited a protective effect on neurons.
基金the Natural Science Foundation of Southwest Medical University(No.2016XNYD217,No.2018-ZRQN-032 and No.2016LZXNYD-G03)the National Natural Science Foundation of China(No.82072780)Sichuan Science and Technology Program(No.2022YFS0630).
文摘Objective Protein disulfide isomerase A2(PDIA2),a member of the protein disulfide isomerase family,plays a key role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds,together with enzymes such as thiol isomerase,oxidase,and reductase.This study investigated the clinical significance and potential functions of PDIA2 in glioma.Methods The expression of PDIA2 in gliomas was explored using The Cancer Genome Atlas and Gene Expression Omnibus databases.We analyzed the clinical characteristics of glioma patients and the prognostic and diagnostic value of PDIA2 expression.Kaplan-Meier and Cox regression analyses were used to examine the effect of PDIA2 expression on overall survival,progression-free interval,and disease-specific survival.Furthermore,we performed Gene Set Enrichment Analysis and immune infiltration analysis to investigate the functions of PDIA2.PDIA2 mRNA and protein expression was evaluated in cell lines and glioma tissues.Results PDIA2 was expressed at low levels in glioma patients.Kaplan-Meier survival analysis showed that glioma patients with low PDIA2 levels had a worse prognosis than those with high PDIA2 levels.Receiver operating characteristic curve analysis indicated the diagnostic and prognostic ability of PDIA2(area under the curve=0.918).Pathways associated with PD1,PI3K/AKT,cancer immunotherapy via PD1 blockade,Fceri-mediated NF-kB activation,FOXM1,and DNA repair were enriched in glioma patients with low levels of PDIA2.PDIA2 expression levels were negatively correlated with immune cell infiltrate levels.Conclusion PDIA2 levels are significantly downregulated in glioma.PDIA2 expression may be a potential biomarker for the diagnosis and prognosis of glioma patients.
文摘Newly synthesized membrane and secretory proteins in cells undergo folding in the endoplasmic reticulum with the introduction of disulfide bonds and acquire the correct three-dimensional structure. Disulfide bonds are especially important for protein folding. It has been thought that formation of protein disulfide bonds in eukaryotes is mainly carried out by an enzyme called protein disulfide isomerase. Proteins, bearing the C-terminus of amino acids sequences with His-Asp-Glu-Leu (HDEL) sequence in yeast, in the endoplasmic reticulum (ER), which is a eukaryotic cellular organelle involved in protein synthesis, processing, and transport, have been considered to recycle between ER and Golgi apparatus. The proposal for this recycling model derives from the study of an HDEL-tagged fusion protein. Here, the localization and oligosaccharide modification of protein disulfide isomerase were investigated in yeast, and showed the first direct evidence that this intrinsic ER protein transports from ER to Golgi. Results suggest that this native protein is also accessible to post-ER enzymes, and yet accumulates in the ER.
基金supported by the National Natural Science Foundation of China(32202253)the Natural Science Foundation of Anhui Higher Education Institutions,China(KJ2020A0102)the Talent Research Project of Anhui Agricultural University,China(rc342001)。
文摘Rice blast,caused by Magnaporthe oryzae,is a fungal disease that causes devastating damage to rice production worldwide.During infection,pathogens secrete effector proteins that modulate plant immunity.Disulfide bond formation catalyzed by protein disulfide isomerases(PDI)is essential for protein folding and maturation.However,the biological function of Pdi1 in M.oryzae has not yet been characterized.In this study,we identified the endoplasmic reticulum(ER)-located protein,MoPdi1,in M.oryzae.MoPdi1 regulates conidiation,cell wall stress,and pathogenicity of M.oryzae.Furthermore,the CGHC active sites in the a and a'redox domain of MoPdi1 were essential for the biological function of MoPDI1.Further tests demonstrated that MoPdi1 was involved in the regulation of ER stress and positively regulated ER phagy.We also found that MoPdi1 interacted with MoHut1.Deletion of MoPDI1 led to the bereft of MoHut1 dimerization,which depends on the formation of disulfide bonds.In addition,MoPdi1 affected the normal secretion of the cytoplasmic effector AVR-Pia.We provided evidence that MoHut1 is important for the vegetative growth,conidiation,and pathogenicity in M.oryzae.Therefore,our findings could provide a suitable target point for designing antifungal agrochemicals against rice blast fungus.
基金Supported by the National Natural Science Foundation of China （21036005）.
文摘Disulfide bond formation protein A （DsbA） is one of the important helper proteins for folding in protein synthesis in vivo. In this study, purification of recombinant DsbA was investigated by examining four important factors with Box-Behnken design method, a statistic-based design of experiments. The optimal operation conditions were obtained by adopting the effectiveness coefficient method on the multi-objective problem, which takes the protein recovery, purification efficiency and throughput of ion-exchange chromatography into account. After the optimization, protein recovery of 96.8% and purity higher than 95% DsbA was achieved, and the productivity was （377.9±1.7） mg soluble DsbA per liter broth. The purified protein was identified by peptide mass fingerprinting matching the record of gil2624856, a mutant of DsbA. The DsbA was preliminarily applied to the refolding of denatured lysozyme in vitro.
基金This work was partially supported by the National Institutes of Health(NCI grant number R01CA222596)Department of Defense(grant number W81XWH-16-1-0203)+1 种基金American Cancer Society(grant number RSG-16-213-01-TBE)Kentucky Lung Cancer Research Program(KLCRP2016).
文摘Correct folding of nascent peptides occurs in the endoplasmic reticulum(ER).It is a complicate process primarily accomplished by the coordination of multiple redox proteins including members of the protein disulfide isomerase(PDI)family.As a critical member of the PDI family,thioredoxin domain containing protein 5(TXNDC5)assists the folding of newly synthesized peptides to their mature form through series of disulfide bond exchange reactions.Interestingly,TXNDC5 is frequently found overexpressed in specimens of many human diseases including various types of cancer.In this review,we summarized the biochemical function of TXNDC5 in mammalian cells and the recent progress on the understanding of its role and molecular mechanisms in cancer development.Findings of TXNDC5 in the activation of intracellular signaling pathways,stimulation of cell growth&proliferation,facilitation of cell survival and modulation of extracellular matrix to affect cancer cell invasion and metastasis are reviewed.These published studies suggest that strategies of targeting TXNDC5 can be developed as potentially valuable methods for the treatment of certain types of cancer in patients.
文摘Protein disulfide isomerases （PDIs） are known to play important roles in the folding of nascent proteins and in the formation of disulfide bonds. Recently, we identified a PDI from Chlamydomonas reinhardtii （CrPDI2） by a mass spectrometry approach that is specifically enriched by heparin affinity chromatography in samples taken during the night phase. Here, we show that the recombinant CrPDI2 is a redox-active protein. It is reduced by thioredoxin reductase and catalyzes itself the reduction of insulin chains and the oxidative refolding of scrambled RNase A. By immunoblots, we confirm a high-amplitude change in abundance of the heparin-bound CrPDI2 during subjective night. Interestingly, we find that CrPDI2 is present in protein complexes of different sizes at both day and night. Among three identified interac- tion partners, one （a 2-cys peroxiredoxin） is present only during the night phase. To study a potential function of CrPDI2 within the circadian system, we have overexpressed its gene. Two transgenic lines were used to measure the rhythm of phototaxis~ In the transgenic strains, a change in the acrophase was observed. This indicates that CrPDI2 is involved in the circadian signaling pathway and, together with the night phase-specific interaction of CrPDI2 and a peroxiredoxin, these findings suggest a close coupling of redox processes and the circadian clock in C. reinhardtii.
