The process of cold acclimation is an important adaptive response whereby many plants from temperate regions increase their freezing tolerance after being exposed to low non-freezing temperatures. The correct developm...The process of cold acclimation is an important adaptive response whereby many plants from temperate regions increase their freezing tolerance after being exposed to low non-freezing temperatures. The correct development of this response relies on proper accumulation of a number of transcription factors that regulate expression patterns of cold-responsive genes. Multiple studies have revealed a variety of molecular mechanisms involved in promoting the accumulation of these transcription factors. Interestingly, however, the mechanisms implicated in controlling such accumulation to ensure their adequate levels remain largely unknown. In this work, we demonstrate that prefoldins （PFDs） control the levels of HY5, an Arabidopsis transcription factor with a key role in cold acclimation by activating anthocyanin biosynthesis, in response to low temperature. Our results show that, under cold conditions, PFDs accumulate into the nucleus through a DELLA-dependent mechanism, where they interact with HY5, triggering its ubiquitination and subsequent degradation. The degradation of HY5 would result, in turn, in anthocyanin biosynthesis attenuation, ensuring the accurate development of cold acclimation. These findings uncover an unanticipated nuclear function for PFDs in plant responses to abiotic stresses.展开更多
During the last years, our understanding of the mechanisms that control plant response to salt stress has been steadily progressing. Pharmacological studies have allowed the suggestion that the cytoskeleton may be inv...During the last years, our understanding of the mechanisms that control plant response to salt stress has been steadily progressing. Pharmacological studies have allowed the suggestion that the cytoskeleton may be involved in regulating such a response. Nevertheless, genetic evidence establishing that the cytoskeleton has a role in plant tolerance to salt stress has not been reported yet. Here, we have characterized Arabidopsis T-DNA mutants for genes encoding proteins orthologous to prefoldin （PFD） subunits 3 and 5 from yeast and mammals. In these organisms, PFD subunits, also known as Genes Involved in Microtubule biogenesis （GIM）, form a heterohexameric PFD complex implicated in tubulin and actin folding. We show that, indeed, PFD3 and PFD5 can substitute for the loss of their yeast orthologs, as they are able to complement yeast gim2Δ and gim5Δ mutants, respectively. Our results indicate that pfd3 and pfd5 mutants have reduced levels of α- and β-tubulin compared to the wild-type plants when growing under both control and salt-stress conditions. In addition, pfd3 and pfd5 mutants display alterations in their developmental patterns and microtubule organization, and, more importantly, are hypersensitive to high concentrations of NaCl but not of LiCl or mannitol. These results demonstrate that the cytoskeleton plays an essential role in plant tolerance to salt stress.展开更多
A molecular dynamics study to investigate the cavity control of Prefoldin based bio nano actuator is presented in this paper. Prefoldin is a molecular chaperone with a jellyfish-like structure containing six long coil...A molecular dynamics study to investigate the cavity control of Prefoldin based bio nano actuator is presented in this paper. Prefoldin is a molecular chaperone with a jellyfish-like structure containing six long coiled-coil tentacles and a large central cavity. We took the temperature and p H of the medium into account,and analyzed the conformational flexibility of the Prefoldin nano actuator in details. Results show that the prefoldin is a very flexible protein, the conformational state of which appears to depend on the temperature and p H values of the medium. In fact, combining these two control parameters, a suitable environment is provided to capture nano cargoes with specific dimensions. These properties of Prefoldin actuator can be used for drug delivery in the body.展开更多
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
Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targe...Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targets.Design Prefoldin(PFDN)is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers.However,whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated.In this study,molecular biology,cell culture,transcriptome sequencing and other experimental techniques,combined with bioinformatics,were used to verify the regulatory effects of PFDN6 on CRC.Results PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC.Knockdown of PFDN6 reduced the tumour cell number,promoted apoptosis,and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines.Mechanistically,differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.Conclusion PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575.These results open new avenues for therapeutic interventions for patients with CRC.展开更多
Gravity-induced root curvature involves the asymmetric distribution of the phytohormone auxin.This response depends on the concerted activities of the auxin transporters such as PIN-FORMED(PIN)proteins for auxin efflu...Gravity-induced root curvature involves the asymmetric distribution of the phytohormone auxin.This response depends on the concerted activities of the auxin transporters such as PIN-FORMED(PIN)proteins for auxin efflux and AUXIN RESISTANT 1(AUX1)for auxin influx.However,how the auxin gradient is established remains elusive.Here we identified a new mutant with a short root,strong auxin distribution in the lateral root cap and an impaired gravitropic response.The causal gene encoded an Arabidopsis homolog of the human unconventional prefoldin RPB5 interactor(URI).At URI interacted with prefoldin 2(PFD2)and PFD6,twoβ-type PFD members that modulate actin and tubulin patterning in roots.The auxin reporter DR5_(rev):GFP showed that asymmetric auxin redistribution after gravistimulation is disordered in aturi-1 root tips.Treatment with the endomembrane protein trafficking inhibitor brefeldin A indicated that recycling of the auxin transporter PIN2 is disrupted in aturi-1 roots as well as in pfd mutants.We propose that At URI cooperates with PFDs to recycle PIN2and modulate auxin distribution.展开更多
文摘The process of cold acclimation is an important adaptive response whereby many plants from temperate regions increase their freezing tolerance after being exposed to low non-freezing temperatures. The correct development of this response relies on proper accumulation of a number of transcription factors that regulate expression patterns of cold-responsive genes. Multiple studies have revealed a variety of molecular mechanisms involved in promoting the accumulation of these transcription factors. Interestingly, however, the mechanisms implicated in controlling such accumulation to ensure their adequate levels remain largely unknown. In this work, we demonstrate that prefoldins （PFDs） control the levels of HY5, an Arabidopsis transcription factor with a key role in cold acclimation by activating anthocyanin biosynthesis, in response to low temperature. Our results show that, under cold conditions, PFDs accumulate into the nucleus through a DELLA-dependent mechanism, where they interact with HY5, triggering its ubiquitination and subsequent degradation. The degradation of HY5 would result, in turn, in anthocyanin biosynthesis attenuation, ensuring the accurate development of cold acclimation. These findings uncover an unanticipated nuclear function for PFDs in plant responses to abiotic stresses.
文摘During the last years, our understanding of the mechanisms that control plant response to salt stress has been steadily progressing. Pharmacological studies have allowed the suggestion that the cytoskeleton may be involved in regulating such a response. Nevertheless, genetic evidence establishing that the cytoskeleton has a role in plant tolerance to salt stress has not been reported yet. Here, we have characterized Arabidopsis T-DNA mutants for genes encoding proteins orthologous to prefoldin （PFD） subunits 3 and 5 from yeast and mammals. In these organisms, PFD subunits, also known as Genes Involved in Microtubule biogenesis （GIM）, form a heterohexameric PFD complex implicated in tubulin and actin folding. We show that, indeed, PFD3 and PFD5 can substitute for the loss of their yeast orthologs, as they are able to complement yeast gim2Δ and gim5Δ mutants, respectively. Our results indicate that pfd3 and pfd5 mutants have reduced levels of α- and β-tubulin compared to the wild-type plants when growing under both control and salt-stress conditions. In addition, pfd3 and pfd5 mutants display alterations in their developmental patterns and microtubule organization, and, more importantly, are hypersensitive to high concentrations of NaCl but not of LiCl or mannitol. These results demonstrate that the cytoskeleton plays an essential role in plant tolerance to salt stress.
文摘A molecular dynamics study to investigate the cavity control of Prefoldin based bio nano actuator is presented in this paper. Prefoldin is a molecular chaperone with a jellyfish-like structure containing six long coiled-coil tentacles and a large central cavity. We took the temperature and p H of the medium into account,and analyzed the conformational flexibility of the Prefoldin nano actuator in details. Results show that the prefoldin is a very flexible protein, the conformational state of which appears to depend on the temperature and p H values of the medium. In fact, combining these two control parameters, a suitable environment is provided to capture nano cargoes with specific dimensions. These properties of Prefoldin actuator can be used for drug delivery in the body.
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supported by Doctoral‘Direct Access’Research Project of Chongqing(CSTB2022BSXM-JCX0012)the National Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0127)the 2023 programme for training talented pilots upon graduation(LHRCYB23009).
文摘Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targets.Design Prefoldin(PFDN)is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers.However,whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated.In this study,molecular biology,cell culture,transcriptome sequencing and other experimental techniques,combined with bioinformatics,were used to verify the regulatory effects of PFDN6 on CRC.Results PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC.Knockdown of PFDN6 reduced the tumour cell number,promoted apoptosis,and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines.Mechanistically,differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.Conclusion PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575.These results open new avenues for therapeutic interventions for patients with CRC.
基金supported by an initiation fund from the Shandong Agricultural University,the National Natural Science Foundation of China(31570291)the Shandong“Foreign experts double hundred”Program(WST2017008)the Natural Science Foundation of Shandong Province(ZR2021MC175)。
文摘Gravity-induced root curvature involves the asymmetric distribution of the phytohormone auxin.This response depends on the concerted activities of the auxin transporters such as PIN-FORMED(PIN)proteins for auxin efflux and AUXIN RESISTANT 1(AUX1)for auxin influx.However,how the auxin gradient is established remains elusive.Here we identified a new mutant with a short root,strong auxin distribution in the lateral root cap and an impaired gravitropic response.The causal gene encoded an Arabidopsis homolog of the human unconventional prefoldin RPB5 interactor(URI).At URI interacted with prefoldin 2(PFD2)and PFD6,twoβ-type PFD members that modulate actin and tubulin patterning in roots.The auxin reporter DR5_(rev):GFP showed that asymmetric auxin redistribution after gravistimulation is disordered in aturi-1 root tips.Treatment with the endomembrane protein trafficking inhibitor brefeldin A indicated that recycling of the auxin transporter PIN2 is disrupted in aturi-1 roots as well as in pfd mutants.We propose that At URI cooperates with PFDs to recycle PIN2and modulate auxin distribution.
