Pub Date : 2023-08-11DOI: 10.33696/signaling.4.099
J. Fu
This paper summarizes the research results of Fu et al. on the pathological mechanism of organ injury. A hypothesis was proposed that "organ injury is a consequence of the activation of the 5-hydroxytryptamine degradation system (5DS) axis in cells". The basic composition of the 5DS axis in cells and the principle of its activation leading to cell lesions were determined. The possibility of treating various organ injury diseases in clinical practice by inhibiting the 5DS axis is discussed.
{"title":"Activation of the 5-hydroxytryptamine Degradation System in Cells and Organ Injury","authors":"J. Fu","doi":"10.33696/signaling.4.099","DOIUrl":"https://doi.org/10.33696/signaling.4.099","url":null,"abstract":"This paper summarizes the research results of Fu et al. on the pathological mechanism of organ injury. A hypothesis was proposed that \"organ injury is a consequence of the activation of the 5-hydroxytryptamine degradation system (5DS) axis in cells\". The basic composition of the 5DS axis in cells and the principle of its activation leading to cell lesions were determined. The possibility of treating various organ injury diseases in clinical practice by inhibiting the 5DS axis is discussed.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78916819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-11DOI: 10.33696/signaling.4.097
A. Mitrofanova, Rachel Njeim, A. Fornoni
Alla Mitrofanova1,2,*, Rachel Njeim1,2, Alessia Fornoni1,2 1Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA 2Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, Florida, USA *Correspondence should be addressed to Alla Mitrofanova, a.mitrofanova@miami.edu
{"title":"The Finer Points of Podocyte Sphingolipid Metabolism in Diabetic Kidney Disease","authors":"A. Mitrofanova, Rachel Njeim, A. Fornoni","doi":"10.33696/signaling.4.097","DOIUrl":"https://doi.org/10.33696/signaling.4.097","url":null,"abstract":"Alla Mitrofanova1,2,*, Rachel Njeim1,2, Alessia Fornoni1,2 1Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA 2Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, Florida, USA *Correspondence should be addressed to Alla Mitrofanova, a.mitrofanova@miami.edu","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86587734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-11DOI: 10.33696/signaling.4.098
N. Matsushima, Hiroki Miyashita, D. Batkhishig, R. Kretsinger
Small leucine rich repeat proteoglycans (SLRPs) exist in the extracellular matrix. SLRPs contain tandem arrays of LRRs flanked by cysteine clusters at the both N- and C-termini. The extreme N- and/or C-termini contain low complexity sequences, glycosaminoglycan (GAG) chain and/or sulfated tyrosine residues in some members of SLRPs. The LRR solenoid structure may be divided into four parts consisting of a concave surface, an ascending surface, a convex surface, and a descending surface. SLRPs share many biological functions including collagen fibrillogenesis, signaling, innate immunity, and inflammation through the binding of various ligands. We undertake a comprehensive literature search of publications in order to make a list of ligands of SLRPs. We describe and discuss the interacting sites of SLRPs to binding partners. The protein-ligand interactions occur on not only the concave surface but also the ascending surface and the N- or C-terminal capping regions. In addition, the extreme N- and/or C-terminal regions with the GAG chains or sulfated tyrosine residues participate in ligand-interactions.
{"title":"Structural Insights into Protein-Ligand Interactions of Small Leucine Rich Repeat Proteoglycans with a Large Number of Binding Partners: An Overview","authors":"N. Matsushima, Hiroki Miyashita, D. Batkhishig, R. Kretsinger","doi":"10.33696/signaling.4.098","DOIUrl":"https://doi.org/10.33696/signaling.4.098","url":null,"abstract":"Small leucine rich repeat proteoglycans (SLRPs) exist in the extracellular matrix. SLRPs contain tandem arrays of LRRs flanked by cysteine clusters at the both N- and C-termini. The extreme N- and/or C-termini contain low complexity sequences, glycosaminoglycan (GAG) chain and/or sulfated tyrosine residues in some members of SLRPs. The LRR solenoid structure may be divided into four parts consisting of a concave surface, an ascending surface, a convex surface, and a descending surface. SLRPs share many biological functions including collagen fibrillogenesis, signaling, innate immunity, and inflammation through the binding of various ligands. We undertake a comprehensive literature search of publications in order to make a list of ligands of SLRPs. We describe and discuss the interacting sites of SLRPs to binding partners. The protein-ligand interactions occur on not only the concave surface but also the ascending surface and the N- or C-terminal capping regions. In addition, the extreme N- and/or C-terminal regions with the GAG chains or sulfated tyrosine residues participate in ligand-interactions.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88284951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-13DOI: 10.33696/signaling.4.096
Lishu Guo
Mitochondrial permeability transition pore (PTP) plays an important role in mitochondrial physiology and cell fate. Emerging studies highlight PTP forms from F-ATP synthase, but whether F-ATP synthase inhibitory factor 1 (IF1) regulates the activity of PTP is basically unknown. We have recently demonstrated that IF1 interacts with p53-CyPD complex and promotes opening of the PTP, and IF1 is necessary for the formation of p53-CyPD complex. IF1, a natural inhibitor of F-ATP synthase, acts as a main driver of metabolic switch to a Warburg phenotype. In this Commentary, we intend to discuss that the PTP may act as an alternative mechanism through which IF1 regulates metabolic reprogramming. The PTP participates in physiological Ca2+/ROS homeostasis and cell fate depending on the open state. The PTP-regulatory role of IF1 provides a clue that IF1 participates in metabolic plasticity probably involving modulation of PTP activity.
{"title":"F-ATP Synthase Inhibitory Factor 1 in Regulation of Mitochondria Permeability Transition Pore and Metabolic Reprogramming","authors":"Lishu Guo","doi":"10.33696/signaling.4.096","DOIUrl":"https://doi.org/10.33696/signaling.4.096","url":null,"abstract":"Mitochondrial permeability transition pore (PTP) plays an important role in mitochondrial physiology and cell fate. Emerging studies highlight PTP forms from F-ATP synthase, but whether F-ATP synthase inhibitory factor 1 (IF1) regulates the activity of PTP is basically unknown. We have recently demonstrated that IF1 interacts with p53-CyPD complex and promotes opening of the PTP, and IF1 is necessary for the formation of p53-CyPD complex. IF1, a natural inhibitor of F-ATP synthase, acts as a main driver of metabolic switch to a Warburg phenotype. In this Commentary, we intend to discuss that the PTP may act as an alternative mechanism through which IF1 regulates metabolic reprogramming. The PTP participates in physiological Ca2+/ROS homeostasis and cell fate depending on the open state. The PTP-regulatory role of IF1 provides a clue that IF1 participates in metabolic plasticity probably involving modulation of PTP activity.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85062793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-31DOI: 10.33696/signaling.4.095
Tahereh Kashkoulinejad-Kouhi
One of the mechanisms used by epigenetic therapy is the elevation of host cell-derived double stranded RNA (dsRNA) baseline levels through overexpression of genomic repetitive elements especially Alu retroelements. The dsRNAs trigger immunogenic responses since immune system cannot distinguish between endogenous and exogenous dsRNAs derived from viral infections; hence called “Viral mimicry response”. These dsRNAs are recognized by pattern recognition receptors (PRRs) such as MDA-5 which further induce inflammatory responses through interferon secretion. However, the response is limited through the function of some editing enzymes such as ADAR1 which destabilizes the formation of dsRNAs and renders the therapy less efficient through attenuating interferon secretion by immune cells. Since, some cancer cells can survive even after ADAR1 inhibition, it is speculated that there might be other mechanism which contribute to dsRNA destabilization. Since dsRNA formation derived from retroelement transcripts mimics viral infections, we tried to review the mechanistic approaches applied during host-pathogen interaction to highlight a possible candidate which might be cogitable for further investigations in epigenetic therapy. dsRNAs produced by RNA viruses are sensed by PRRs and activate nuclear factor erythroid 2 p45-related factor 2 (NRF2) which further downregulates STING protein and attenuates IFN release. RNA viruses such as SARS-CoV-2 have the potential to impair NRF2 signaling and eliminate its inhibitory effect from STING, leading to excessive release of IFNs and destroy pulmonary cells through cytokine release storm (CRS). Here, we briefly explain that NRF2, in a very downstream side of anti-viral response, might be a potential candidate target in combination with epigenetic therapy to circumvent the limitations in cancer epigenetic therapy.
{"title":"Improving Cancer Epigenetic Therapy; A Glimpse of NRF2","authors":"Tahereh Kashkoulinejad-Kouhi","doi":"10.33696/signaling.4.095","DOIUrl":"https://doi.org/10.33696/signaling.4.095","url":null,"abstract":"One of the mechanisms used by epigenetic therapy is the elevation of host cell-derived double stranded RNA (dsRNA) baseline levels through overexpression of genomic repetitive elements especially Alu retroelements. The dsRNAs trigger immunogenic responses since immune system cannot distinguish between endogenous and exogenous dsRNAs derived from viral infections; hence called “Viral mimicry response”. These dsRNAs are recognized by pattern recognition receptors (PRRs) such as MDA-5 which further induce inflammatory responses through interferon secretion. However, the response is limited through the function of some editing enzymes such as ADAR1 which destabilizes the formation of dsRNAs and renders the therapy less efficient through attenuating interferon secretion by immune cells. Since, some cancer cells can survive even after ADAR1 inhibition, it is speculated that there might be other mechanism which contribute to dsRNA destabilization. Since dsRNA formation derived from retroelement transcripts mimics viral infections, we tried to review the mechanistic approaches applied during host-pathogen interaction to highlight a possible candidate which might be cogitable for further investigations in epigenetic therapy. dsRNAs produced by RNA viruses are sensed by PRRs and activate nuclear factor erythroid 2 p45-related factor 2 (NRF2) which further downregulates STING protein and attenuates IFN release. RNA viruses such as SARS-CoV-2 have the potential to impair NRF2 signaling and eliminate its inhibitory effect from STING, leading to excessive release of IFNs and destroy pulmonary cells through cytokine release storm (CRS). Here, we briefly explain that NRF2, in a very downstream side of anti-viral response, might be a potential candidate target in combination with epigenetic therapy to circumvent the limitations in cancer epigenetic therapy.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88570470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-18DOI: 10.33696/signaling.4.094
P. Jain
Bacterium maintains its pathogenicity in the host by continuing replication and adopting temporal and spatial coordination of cell division steps such as cell wall synthesis, DNA replication, chromosome segregation, Z ring assembly, septum formation and finally cytokinesis. This multistep process requires spatiotemporal assembly of macromolecular complexes and is probably regulated by redundant and multifunctional activities of cell replication and division proteins. Two macromolecular assemblies of peptidoglycan biosynthesis, known as elongasome and divisome are known to drive the division of mother cell into two daughter cells and are characterized by the presence of signature protein complexes. Though the exact composition of macromolecular complexes is yet to be defined in Mycobacterium, the presence of some conserved proteins demonstrates the preservation of elementary units. Along with elongasome and divisome complexes, chromosome replication and segregation proteins are very important to understand as these proteins are very essential for bacilli survival, sustenance, and pathogenesis. In this review, along with presenting the differential features of Mycobacterium cell division process, we are comparing chromosome replication and segregation proteins of Mycobacterium with other bacterial species as we aim to identify structural and functional differences between these proteins in different species. In this review, we have also listed the potential drugs that can be tested to target Mycobacterium chromosome replication and segregation proteins. We expect that based on these differences identified, researchers would be able to direct their research in the characterization of Mycobacterium specific drug.
{"title":"Understanding Chromosome Replication and Segregation Unit of Mycobacterium and Its Comparative Analysis with Model Organisms: From Drug Targets to Drug Identification","authors":"P. Jain","doi":"10.33696/signaling.4.094","DOIUrl":"https://doi.org/10.33696/signaling.4.094","url":null,"abstract":"Bacterium maintains its pathogenicity in the host by continuing replication and adopting temporal and spatial coordination of cell division steps such as cell wall synthesis, DNA replication, chromosome segregation, Z ring assembly, septum formation and finally cytokinesis. This multistep process requires spatiotemporal assembly of macromolecular complexes and is probably regulated by redundant and multifunctional activities of cell replication and division proteins. Two macromolecular assemblies of peptidoglycan biosynthesis, known as elongasome and divisome are known to drive the division of mother cell into two daughter cells and are characterized by the presence of signature protein complexes. Though the exact composition of macromolecular complexes is yet to be defined in Mycobacterium, the presence of some conserved proteins demonstrates the preservation of elementary units. Along with elongasome and divisome complexes, chromosome replication and segregation proteins are very important to understand as these proteins are very essential for bacilli survival, sustenance, and pathogenesis. In this review, along with presenting the differential features of Mycobacterium cell division process, we are comparing chromosome replication and segregation proteins of Mycobacterium with other bacterial species as we aim to identify structural and functional differences between these proteins in different species. In this review, we have also listed the potential drugs that can be tested to target Mycobacterium chromosome replication and segregation proteins. We expect that based on these differences identified, researchers would be able to direct their research in the characterization of Mycobacterium specific drug.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72916634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-18DOI: 10.33696/signaling.4.093
Shantanu Shrivastava, Nimisha Bhatu
Most medicines and supplements which include probiotics have both expected clinical outcomes and unwanted side effects, which plays a major role when considering them as a mode of treatment. This review is an update about the advantages and disadvantages associated with the use of probiotics as part of a safe therapeutic armamentarium in health and other diseases. The advantages of probiotics run across multiple tissue systems in the body and a has a wide age spectrum. Probiotics also promote cardiovascular health, accelerate recovery from the condition of antibiotic-associated diarrhoea, decrease the effect of necrotizing enterocolitis with reduced inflammation, and accelerate the healing of the wound. Probiotics also contribute in treating chronic diseases for patients with type 2 diabetes as well as patients with HIV/AIDS. Moreover, probiotics play an important role in the treatment and/or prevention of cancers, especially those of the colon and bladder. On the other hand, probiotics also mimic serious threats to immunocompromised, genetically predisposed bodies, children, and newborns. Using probiotics may lead to bacteremia, fungemia, or septicemia when consumed more. Also, probiotics are found as a causative agent for pneumonia and abdominal abscesses, increase platelet aggregation, and promote antibiotic resistance among others. A huge number of microorganisms inhabit the human gut and consequently cause a compound network of the interactions of those organisms with each other and within the host cells, which stresses the requirement of extra caution in the use of probiotics as treatment therapy.
{"title":"A Study on the Usage of Probiotics as a Safer Antipyretic","authors":"Shantanu Shrivastava, Nimisha Bhatu","doi":"10.33696/signaling.4.093","DOIUrl":"https://doi.org/10.33696/signaling.4.093","url":null,"abstract":"Most medicines and supplements which include probiotics have both expected clinical outcomes and unwanted side effects, which plays a major role when considering them as a mode of treatment. This review is an update about the advantages and disadvantages associated with the use of probiotics as part of a safe therapeutic armamentarium in health and other diseases. The advantages of probiotics run across multiple tissue systems in the body and a has a wide age spectrum. Probiotics also promote cardiovascular health, accelerate recovery from the condition of antibiotic-associated diarrhoea, decrease the effect of necrotizing enterocolitis with reduced inflammation, and accelerate the healing of the wound. Probiotics also contribute in treating chronic diseases for patients with type 2 diabetes as well as patients with HIV/AIDS. Moreover, probiotics play an important role in the treatment and/or prevention of cancers, especially those of the colon and bladder. On the other hand, probiotics also mimic serious threats to immunocompromised, genetically predisposed bodies, children, and newborns. Using probiotics may lead to bacteremia, fungemia, or septicemia when consumed more. Also, probiotics are found as a causative agent for pneumonia and abdominal abscesses, increase platelet aggregation, and promote antibiotic resistance among others. A huge number of microorganisms inhabit the human gut and consequently cause a compound network of the interactions of those organisms with each other and within the host cells, which stresses the requirement of extra caution in the use of probiotics as treatment therapy.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79095326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-18DOI: 10.33696/signaling.4.092
J. Kumar, Prachi Gholap, T. Pillai
In accordance with the present epidemiological paradigm, viral mutations of the virus are on the rise, and their natural effects are being selected for at a higher rate than normal. According to the World Health Organization (WHO), the global COVID-19 pandemic induced by the Delta and Omicron strain of the SARS-CoV-2 virus could propagate and disseminate more rapidly than other viruses thanks to its many mutations, and these also caused some very significant health problems. The established medications would eventually start to lose their efficacy since the variation mutated more quickly than the original stain. As protein spikes are the point of origin or epitome for the mutations to take place, it would be most effective to target the remaining vital enzymes by binding the proteins with the largest pocket sizes. The objective of the current work is to employ in-silico analysis to discover the streptomyces chemicals that suppress the SARS-CoV-2 virus as well as its mutated strains thus promoting a healthy body. Based on the drug likeness property of compounds when subjected to molecular docking, a total of 14 compounds were identified and selected from the PUBCHEM database that showed highest binding energy with the targeted Receptor Binding Domain. The compounds namely - Streptomyces tanashiensis; Thaxtomin A; Bafilomycin A1 from Streptomyces griseus and few others as mentioned further on more research would support and confirm the utilizing of these to create new medications to treat the novel SARS-CoV-2 infectious strains.
{"title":"Novel Drug Development for Treatment of COVID-19 by In Silico Analysis: Identification of SARS-Cov-2 Inhibiting Streptomyces Compounds","authors":"J. Kumar, Prachi Gholap, T. Pillai","doi":"10.33696/signaling.4.092","DOIUrl":"https://doi.org/10.33696/signaling.4.092","url":null,"abstract":"In accordance with the present epidemiological paradigm, viral mutations of the virus are on the rise, and their natural effects are being selected for at a higher rate than normal. According to the World Health Organization (WHO), the global COVID-19 pandemic induced by the Delta and Omicron strain of the SARS-CoV-2 virus could propagate and disseminate more rapidly than other viruses thanks to its many mutations, and these also caused some very significant health problems. The established medications would eventually start to lose their efficacy since the variation mutated more quickly than the original stain. As protein spikes are the point of origin or epitome for the mutations to take place, it would be most effective to target the remaining vital enzymes by binding the proteins with the largest pocket sizes. The objective of the current work is to employ in-silico analysis to discover the streptomyces chemicals that suppress the SARS-CoV-2 virus as well as its mutated strains thus promoting a healthy body. Based on the drug likeness property of compounds when subjected to molecular docking, a total of 14 compounds were identified and selected from the PUBCHEM database that showed highest binding energy with the targeted Receptor Binding Domain. The compounds namely - Streptomyces tanashiensis; Thaxtomin A; Bafilomycin A1 from Streptomyces griseus and few others as mentioned further on more research would support and confirm the utilizing of these to create new medications to treat the novel SARS-CoV-2 infectious strains.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90754645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.33696/signaling.4.091
Miaoling Tang, Rongni Feng, Jun Yu Li
Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing morbidity and mortality worldwide. The migration and motility of HCC tumor cells are enhanced by the formation of invadopodia, which comprise membrane protrusions at the leading edge. Previous studies have showed that cell division cycle 42 (CDC42) plays an essential role in remodeling the cytoskeleton, which is associated with invadopodia formation and thus mediates cellular movement. Therefore, aberrant expression of CDC42 is hypothesized to promote tumor cell migration. In this review, we discuss the important role of CDC42 activation induced by guanine nucleotide-exchange factors (GEFs), which function as upstream regulators to activate CDC42, thereby mediating HCC invasion and metastasis by facilitating invadopodia formation. Furthermore, inhibitors targeting the CDC42-GEF interaction might be developed as an intervention against HCC metastasis.
{"title":"Potential Mechanism of CDC42 Promoting HCC Metastasis","authors":"Miaoling Tang, Rongni Feng, Jun Yu Li","doi":"10.33696/signaling.4.091","DOIUrl":"https://doi.org/10.33696/signaling.4.091","url":null,"abstract":"Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing morbidity and mortality worldwide. The migration and motility of HCC tumor cells are enhanced by the formation of invadopodia, which comprise membrane protrusions at the leading edge. Previous studies have showed that cell division cycle 42 (CDC42) plays an essential role in remodeling the cytoskeleton, which is associated with invadopodia formation and thus mediates cellular movement. Therefore, aberrant expression of CDC42 is hypothesized to promote tumor cell migration. In this review, we discuss the important role of CDC42 activation induced by guanine nucleotide-exchange factors (GEFs), which function as upstream regulators to activate CDC42, thereby mediating HCC invasion and metastasis by facilitating invadopodia formation. Furthermore, inhibitors targeting the CDC42-GEF interaction might be developed as an intervention against HCC metastasis.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"173 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76511173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: An indispensable member of the Rho family, RhoB is an isoprenylated small GTPases that modulate the cellular cytoskeletal organization. While DNA gets damaged, it takes part in the neoplastic apoptotic mechanism. In this study, we evaluated the structure of Rho-related GTP-binding protein RhoB due to the unavailability of 3D structure in the protein data bank database. Results: The expected pI value of RhoB was 5.10 (acidic). The target–template alignment was computed using the GMQE value meanwhile 6hxu.1.A from Homo sapiens was selected as the template structure. The Swiss model was exploited to complete the model construction task. The structural compatibility and stability were revealed after a 100ns molecular dynamics simulation using GROMACA employing the OPLS-AA force field. Based on their fluctuating activity and their location between 100 and 110 and 140 and 150, PCA analysis discovered relevant residues. Conclusion: By providing an insight into the biophysical phenomenon of Rho-related GTP-binding protein RhoB inhibitors, this study will assist future investigations addressing the relationship between gene mutation and abnormalities produced by protein Rho-related GTP-binding protein RhoB in apoptotic events.
{"title":"A Computational Investigation on Rho-related GTP-binding Protein RhoB through Molecular Modeling and Molecular Dynamics Simulation Study","authors":"Shamrat Kumar Paul, Chowdhury Lutfun Nahar Metu, Sunita Kumari Sutihar, Md. Saddam, Bristi Paul, Md. Lutful Kabir, Md. Mostofa Uddin Helal","doi":"10.33696/signaling.4.089","DOIUrl":"https://doi.org/10.33696/signaling.4.089","url":null,"abstract":"Background: An indispensable member of the Rho family, RhoB is an isoprenylated small GTPases that modulate the cellular cytoskeletal organization. While DNA gets damaged, it takes part in the neoplastic apoptotic mechanism. In this study, we evaluated the structure of Rho-related GTP-binding protein RhoB due to the unavailability of 3D structure in the protein data bank database. Results: The expected pI value of RhoB was 5.10 (acidic). The target–template alignment was computed using the GMQE value meanwhile 6hxu.1.A from Homo sapiens was selected as the template structure. The Swiss model was exploited to complete the model construction task. The structural compatibility and stability were revealed after a 100ns molecular dynamics simulation using GROMACA employing the OPLS-AA force field. Based on their fluctuating activity and their location between 100 and 110 and 140 and 150, PCA analysis discovered relevant residues. Conclusion: By providing an insight into the biophysical phenomenon of Rho-related GTP-binding protein RhoB inhibitors, this study will assist future investigations addressing the relationship between gene mutation and abnormalities produced by protein Rho-related GTP-binding protein RhoB in apoptotic events.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"95 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135278556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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