Background/aims: Many questions in cancer biology remain unanswered. Perhaps the most important issues remaining to be addressed focus on the molecular basis of carcinogenesis. Today's cancer focus lies on genetics and gene expression, which is unlikely to explain the true cause of most cancers or lead to a cure.
Methods: Earlier, we provided a plausible mechanism for this process, specifically, that most cancers develop in response to pathogenic stimuli that induce chronic inflammation, fibrosis, and remodeling of the cellular microenvironment. Collectively, these changes generate a precancerous niche (PCN) in which fibrosis and remodeling are ongoing secondary to persistent inflammation, followed by the deployment of a chronic stress escape strategy (CSES). If the CSES is unsuccessful, the cell undergoes a normal cell to cancer cell transformation (NCCT).
Results: Here, we highlight the critical role of fibroblasts as the first cells to undergo neoplastic transformation to a cancerous phenotype which is based on several critical findings. First, persistent disruption of homeostatic crosstalk increases lysyl oxidase activity and lysine oxidation which leads to increased collagen stiffness and decreased elasticity. If unresolved, chronic tissue stress will lead to an escape strategy that involves the recruitment of fibroblasts and fibrocytes from the bone marrow as well as cells undergoing an epithelial-mesenchymal transition (EMT). This yields a heterogeneous pool of cells that express both epithelial and mesenchymal markers and that will ultimately differentiate into cancer-associated fibroblasts (CAFs). Finally, CAFs undergo a mesenchymalepithelial transition (MET) and express epithelial markers that facilitate their integration into the target tissue.
Conclusion: Here, we review the published findings that led us to this conclusion which is the most plausible answer to this critical question.
{"title":"Epistemology of the Origin of Cancer II: Fibroblasts Are the First Cells to Undergo Neoplastic Transformation.","authors":"Björn L D M Brücher, Ijaz S Jamall","doi":"10.33594/000000672","DOIUrl":"10.33594/000000672","url":null,"abstract":"<p><strong>Background/aims: </strong>Many questions in cancer biology remain unanswered. Perhaps the most important issues remaining to be addressed focus on the molecular basis of carcinogenesis. Today's cancer focus lies on genetics and gene expression, which is unlikely to explain the true cause of most cancers or lead to a cure.</p><p><strong>Methods: </strong>Earlier, we provided a plausible mechanism for this process, specifically, that most cancers develop in response to pathogenic stimuli that induce chronic inflammation, fibrosis, and remodeling of the cellular microenvironment. Collectively, these changes generate a precancerous niche (PCN) in which fibrosis and remodeling are ongoing secondary to persistent inflammation, followed by the deployment of a chronic stress escape strategy (CSES). If the CSES is unsuccessful, the cell undergoes a normal cell to cancer cell transformation (NCCT).</p><p><strong>Results: </strong>Here, we highlight the critical role of fibroblasts as the first cells to undergo neoplastic transformation to a cancerous phenotype which is based on several critical findings. First, persistent disruption of homeostatic crosstalk increases lysyl oxidase activity and lysine oxidation which leads to increased collagen stiffness and decreased elasticity. If unresolved, chronic tissue stress will lead to an escape strategy that involves the recruitment of fibroblasts and fibrocytes from the bone marrow as well as cells undergoing an epithelial-mesenchymal transition (EMT). This yields a heterogeneous pool of cells that express both epithelial and mesenchymal markers and that will ultimately differentiate into cancer-associated fibroblasts (CAFs). Finally, CAFs undergo a mesenchymalepithelial transition (MET) and express epithelial markers that facilitate their integration into the target tissue.</p><p><strong>Conclusion: </strong>Here, we review the published findings that led us to this conclusion which is the most plausible answer to this critical question.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 6","pages":"512-537"},"PeriodicalIF":0.0,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039547","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}
Cell senescence was considered an attribute of normal dividing cells, which distinguishing them from cancer cells that do not have a division limit. However, recent studies show that senescence could also occur in cancer cells. Cancer cell senescence could occur as a result of chemotherapy, radiation, inhibition of telomerase activity, induction of DNA damage, changes in the tumor microenvironment, regulation of senescence-related proteins, oxidative stress, inflammation, or epigenetic dysregulation. It seems that the induction of senescence in cancer cells could significantly affect the inhibition of tumor progression, but in some types of cancer, it can affect their invasive character. Furthermore, considering the therapeutic implications of this process, it is essential to consider the positive and negative aspects of cancer cell senescence. It is crucial to understand the molecular mechanisms that induce senescence under specific conditions, considering the potential hazards. In the future, the senescence of cancer cells may contribute to using this property in modern cancer treatment strategies.
{"title":"Mechanisms of Senescence in Cancer: Positive and Negative Aspects of Cancer Cells Senescence","authors":"","doi":"10.33594/000000671","DOIUrl":"https://doi.org/10.33594/000000671","url":null,"abstract":"Cell senescence was considered an attribute of normal dividing cells, which distinguishing them from cancer cells that do not have a division limit. However, recent studies show that senescence could also occur in cancer cells. Cancer cell senescence could occur as a result of chemotherapy, radiation, inhibition of telomerase activity, induction of DNA damage, changes in the tumor microenvironment, regulation of senescence-related proteins, oxidative stress, inflammation, or epigenetic dysregulation. It seems that the induction of senescence in cancer cells could significantly affect the inhibition of tumor progression, but in some types of cancer, it can affect their invasive character. Furthermore, considering the therapeutic implications of this process, it is essential to consider the positive and negative aspects of cancer cell senescence. It is crucial to understand the molecular mechanisms that induce senescence under specific conditions, considering the potential hazards. In the future, the senescence of cancer cells may contribute to using this property in modern cancer treatment strategies.","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"49 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138597767","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/aims: Currently, it is proven that the cellular metabolism of nitric oxide is necessary to maintain optimal health and adaptation of the organism to the impact of various environmental factors. The aim of this work was to reveal the biological role of nitric oxide, its metabolic changes, and its mechanism of action in tissues under hypoxia, as well as the possibility of tissue metabolism correction through NO-dependent systems under the influence of Krebs cycle intermediates.
Methods: A systematic assessment of the effect of succinate (SC, 50 mg/kg b.w.) and α-ketoglutarate (KGL, 50 mg/kg b.w.) in the regulation of oxygendependent processes in rats (mitochondrial oxidative phosphorylation, microsomal oxidation, intensity of lipid peroxidation processes, and the state of the antioxidant defense system) depending on functional changes in nitric oxide production during hypoxia was evaluated. The state of the nitric oxide system was estimated spectrophotometrically by determination of the concentration of its stable nitrite anion metabolite (NO2 -). The levels of catecholamines were estimated from the content of epinephrine and norepinephrine using the differentially fluorescent method. The activity of cytochrome P450-dependent aminopyrine-N-demethylase was determined with the Nash reagent.
Results: Tissue hypoxia and metabolic disorders caused by this condition through changes in the content of catecholamines (epinephrine, norepinephrine, dopamine, DOPA) as well as the cholinesterase-related system (acetylcholine content and acetylcholinesterase activity) were the studied experimental parameters under acute hypoxia (AH, 7% O2 in N2, 30 min). The activation of lipid peroxidation and oxidatively modified proteins and an increase in the epinephrine content in AH are associated with an increased role of SC and a decrease in KGL as substrates of oxidation in mitochondria. A more pronounced effect of exogenous KGL, compared to SC, on the content of nitrite anion as a stable metabolite of nitric oxide in the liver under acute hypoxia against the background of a decrease in the intensity of lipid peroxidation processes was revealed. The activation of SC-dependent mitochondrial oxidative processes caused by AH was found to decrease in animals after an intermittent hypoxia training (IHT) course. IHT (7% O2 in N2, 15-min, 5 times daily, 14 days) prevented the activation of oxidative stress in tissues and blood after the AH impact and increased the efficiency of energy-related reactions in the functioning of hepatic mitochondria through increased oxidation of KGL.
Conclusion: The studied effects of adaptation are mediated by an increase in the role of NO-dependent mechanisms, as assessed by changes in the pool of nitrates, nitrites, carbamides, and total polyamines.
背景/目的:目前已经证明,一氧化氮的细胞代谢是维持机体最佳健康和适应各种环境因素影响所必需的。本研究旨在揭示缺氧条件下一氧化氮的生物学作用、代谢变化及其在组织中的作用机制,以及在克雷布斯循环中间体的影响下,一氧化氮依赖系统对组织代谢进行校正的可能性。方法:系统评估琥珀酸盐(SC, 50 mg/kg b.w.)和α-酮戊二酸盐(KGL, 50 mg/kg b.w.)对缺氧时一氧化氮生成的功能变化对大鼠氧依赖过程(线粒体氧化磷酸化、微粒体氧化、脂质过氧化过程强度和抗氧化防御系统状态)的调节作用。用分光光度法测定其稳定的亚硝酸盐阴离子代谢物(NO2 -)的浓度来估计一氧化氮体系的状态。儿茶酚胺的水平是用差异荧光法从肾上腺素和去甲肾上腺素的含量来估计的。采用Nash试剂测定细胞色素p450依赖性氨基吡啶- n -去甲基化酶的活性。结果:研究急性缺氧(AH, 7% O2 in N2, 30min)下组织缺氧及由此引起的儿茶酚胺(肾上腺素、去甲肾上腺素、多巴胺、多巴胺)含量变化及胆碱酯酶相关系统(乙酰胆碱含量和乙酰胆碱酯酶活性)代谢紊乱的实验参数。AH中脂质过氧化和氧化修饰蛋白的激活以及肾上腺素含量的增加与SC作为线粒体氧化底物的作用增加和KGL的减少有关。与SC相比,外源性KGL对急性缺氧下肝脏中一氧化氮的稳定代谢物亚硝酸盐阴离子含量的影响更为明显,其背景是脂质过氧化过程的强度降低。间歇性缺氧训练(IHT)后,发现AH引起的sc依赖性线粒体氧化过程的激活减少。IHT (7% O2在N2中,15分钟,每天5次,14天)阻止AH冲击后组织和血液中氧化应激的激活,并通过增加KGL的氧化提高肝线粒体功能中能量相关反应的效率。结论:通过硝酸盐、亚硝酸盐、氨酰胺和总多胺的变化来评估,所研究的适应效应是由no依赖机制的作用增加介导的。
{"title":"Do the Effects of Krebs Cycle Intermediates on Oxygen-Dependent Processes in Hypoxia Mediated by the Nitric Oxide System Have Reciprocal or Competitive Relationships?","authors":"Natalia Kurhaluk, Oleksandr Lukash, Halina Tkaczenko","doi":"10.33594/000000669","DOIUrl":"10.33594/000000669","url":null,"abstract":"<p><strong>Background/aims: </strong>Currently, it is proven that the cellular metabolism of nitric oxide is necessary to maintain optimal health and adaptation of the organism to the impact of various environmental factors. The aim of this work was to reveal the biological role of nitric oxide, its metabolic changes, and its mechanism of action in tissues under hypoxia, as well as the possibility of tissue metabolism correction through NO-dependent systems under the influence of Krebs cycle intermediates.</p><p><strong>Methods: </strong>A systematic assessment of the effect of succinate (SC, 50 mg/kg b.w.) and α-ketoglutarate (KGL, 50 mg/kg b.w.) in the regulation of oxygendependent processes in rats (mitochondrial oxidative phosphorylation, microsomal oxidation, intensity of lipid peroxidation processes, and the state of the antioxidant defense system) depending on functional changes in nitric oxide production during hypoxia was evaluated. The state of the nitric oxide system was estimated spectrophotometrically by determination of the concentration of its stable nitrite anion metabolite (NO<sub>2</sub> -). The levels of catecholamines were estimated from the content of epinephrine and norepinephrine using the differentially fluorescent method. The activity of cytochrome P450-dependent aminopyrine-N-demethylase was determined with the Nash reagent.</p><p><strong>Results: </strong>Tissue hypoxia and metabolic disorders caused by this condition through changes in the content of catecholamines (epinephrine, norepinephrine, dopamine, DOPA) as well as the cholinesterase-related system (acetylcholine content and acetylcholinesterase activity) were the studied experimental parameters under acute hypoxia (AH, 7% O<sub>2</sub> in N<sub>2</sub>, 30 min). The activation of lipid peroxidation and oxidatively modified proteins and an increase in the epinephrine content in AH are associated with an increased role of SC and a decrease in KGL as substrates of oxidation in mitochondria. A more pronounced effect of exogenous KGL, compared to SC, on the content of nitrite anion as a stable metabolite of nitric oxide in the liver under acute hypoxia against the background of a decrease in the intensity of lipid peroxidation processes was revealed. The activation of SC-dependent mitochondrial oxidative processes caused by AH was found to decrease in animals after an intermittent hypoxia training (IHT) course. IHT (7% O<sub>2</sub> in N<sub>2</sub>, 15-min, 5 times daily, 14 days) prevented the activation of oxidative stress in tissues and blood after the AH impact and increased the efficiency of energy-related reactions in the functioning of hepatic mitochondria through increased oxidation of KGL.</p><p><strong>Conclusion: </strong>The studied effects of adaptation are mediated by an increase in the role of NO-dependent mechanisms, as assessed by changes in the pool of nitrates, nitrites, carbamides, and total polyamines.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 6","pages":"426-451"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648559","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/aims: All body functions are activated, synchronized and controlled by a substantial, complex network, the nervous system. Upon injury, pathophysiology of the nerve injury proceeds through different paths. The axon may undergo a degenerative retraction from the site of injury for a short distance unless the injury is near to the cell body, in which case it continues to the soma and undergoes retrograde neuronal degeneration. Otherwise, the distal section suffers from Wallerian degeneration, which is marked by axonal swelling, spheroids, and cytoskeleton degeneration. The objective of the study was to evaluate the potential of mesenchymal stem cell laden neural scaffold and insulin-like growth factor I (IGF-I) in nerve regeneration following sciatic nerve injury in a rat model.
Methods: The animals were anaesthetized and a cranio-lateral incision over left thigh was made. Sciatic nerve was exposed and crush injury was introduced for 90 seconds using haemostat at second locking position. The muscle and skin were sutured in routine fashion and thus the rat model of sciatic crush injury was prepared. The animal models were equally distributed into 5 different groups namely A, B, C, D and E and treated with phosphate buffer saline (PBS), carbon nanotubes based neural scaffold only, scaffold with IGF-I, stem cell laden scaffold and stem cell laden scaffold with IGF-I respectively. In vitro scaffold testing was performed. The nerve regeneration was assessed based on physico-neuronal, biochemical, histopathological examination, and relative expression of NRP-1, NRP-2 and GAP-43 and scanning electron microscopy.
Results: Sciatic nerve injury model with crush injury produced for 90 seconds was standardized and successfully used in this study. All the biochemical parameters were in normal range in all the groups indicating no scaffold related changes. Physico-neuronal, histopathological, relative gene expression and scanning electron microscopy observations revealed appreciable nerve regeneration in groups E and D, followed by C and B. Restricted to no regeneration was observed in group A.
Conclusion: Carbon nanotubes based scaffold provided electro-conductivity for proper neuronal regeneration while rat bone marrow-derived mesenchymal stem cells were found to induce axonal sprouting, cellular transformation; whereas IGF-I induced stem cell differentiation, myelin synthesis, angiogenesis and muscle differentiation.
{"title":"Evaluation of Stem Cell Laden Collagen + Polycaprolactone + Multi-Walled Carbon Nano-Tubes Nano-Neural Scaffold with and Without Insulin Like Growth Factor-I For Sciatic Nerve Regeneration Post Crush Injury in Wistar Rats.","authors":"Mamta Mishra, Swapan Kumar Maiti, Kalaiselvan Elangovan, Shivaraju Shivaramu, Karam Pal Singh, Amitha Banu S, Merlin Mamachan, Manish Arya, Divya Mishra, Jurgen Hescheler","doi":"10.33594/000000670","DOIUrl":"10.33594/000000670","url":null,"abstract":"<p><strong>Background/aims: </strong>All body functions are activated, synchronized and controlled by a substantial, complex network, the nervous system. Upon injury, pathophysiology of the nerve injury proceeds through different paths. The axon may undergo a degenerative retraction from the site of injury for a short distance unless the injury is near to the cell body, in which case it continues to the soma and undergoes retrograde neuronal degeneration. Otherwise, the distal section suffers from Wallerian degeneration, which is marked by axonal swelling, spheroids, and cytoskeleton degeneration. The objective of the study was to evaluate the potential of mesenchymal stem cell laden neural scaffold and insulin-like growth factor I (IGF-I) in nerve regeneration following sciatic nerve injury in a rat model.</p><p><strong>Methods: </strong>The animals were anaesthetized and a cranio-lateral incision over left thigh was made. Sciatic nerve was exposed and crush injury was introduced for 90 seconds using haemostat at second locking position. The muscle and skin were sutured in routine fashion and thus the rat model of sciatic crush injury was prepared. The animal models were equally distributed into 5 different groups namely A, B, C, D and E and treated with phosphate buffer saline (PBS), carbon nanotubes based neural scaffold only, scaffold with IGF-I, stem cell laden scaffold and stem cell laden scaffold with IGF-I respectively. In vitro scaffold testing was performed. The nerve regeneration was assessed based on physico-neuronal, biochemical, histopathological examination, and relative expression of NRP-1, NRP-2 and GAP-43 and scanning electron microscopy.</p><p><strong>Results: </strong>Sciatic nerve injury model with crush injury produced for 90 seconds was standardized and successfully used in this study. All the biochemical parameters were in normal range in all the groups indicating no scaffold related changes. Physico-neuronal, histopathological, relative gene expression and scanning electron microscopy observations revealed appreciable nerve regeneration in groups E and D, followed by C and B. Restricted to no regeneration was observed in group A.</p><p><strong>Conclusion: </strong>Carbon nanotubes based scaffold provided electro-conductivity for proper neuronal regeneration while rat bone marrow-derived mesenchymal stem cells were found to induce axonal sprouting, cellular transformation; whereas IGF-I induced stem cell differentiation, myelin synthesis, angiogenesis and muscle differentiation.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 6","pages":"452-477"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396594","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}
Katarzyna Wieczorek-Szukala, Monika Markiewicz, Anna Walczewska, Emilia Zgorzynska
Background/aims: Microglial cells play a crucial role in the development of neuroinflammation in response to harmful stimuli, such as infection, ischemia or injury. Their chronic activation, however, is associated with a progression of neurodegenerative diseases. Therefore, looking for potential factors limiting microglial activation, the effect of docosahexaenoic acid (DHA) on the inflammatory response and TREM2-dependent phagocytic activity in microglia was investigated.
Methods: In LPS-induced primary microglia preincubated with DHA, or without preincubation the expression of ATF3 and TREM2 genes and TREM2, Syk, Akt proteins were determined by RT-PCR and WB, respectively. Cell viability was assayed by MTT and cytokine and chemokine expression was determined by the Proteome Profiler assay. Moreover, the phagocytic activity of microglia was assayed using immunofluorescence.
Results: We found that DHA significantly increased the expression of ATF3 , and decreased the levels of CINC-1, CINC-2αβ, CINC-3 chemokines, IL-1α and IL-1β cytokines, and ICAM-1 adhesion protein. Additionally, preincubation of microglia with DHA resulted in increased Src/Syk kinases activation associated with increased phagocytic microglia activity.
Conclusion: These findings indicate that DHA efficiently inhibits ATF3-dependent release of proinflammatory mediators and enhances phagocytic activity of microglia. The study provides a new mechanism of DHA action in reactive microglia, which may help limit neuronal damage caused by the pro-inflammatory milieu in the brain.
{"title":"Docosahexaenoic Acid (DHA) Reduces LPS-Induced Inflammatory Response Via ATF3 Transcription Factor and Stimulates Src/Syk Signaling-Dependent Phagocytosis in Microglia.","authors":"Katarzyna Wieczorek-Szukala, Monika Markiewicz, Anna Walczewska, Emilia Zgorzynska","doi":"10.33594/000000668","DOIUrl":"10.33594/000000668","url":null,"abstract":"<p><strong>Background/aims: </strong>Microglial cells play a crucial role in the development of neuroinflammation in response to harmful stimuli, such as infection, ischemia or injury. Their chronic activation, however, is associated with a progression of neurodegenerative diseases. Therefore, looking for potential factors limiting microglial activation, the effect of docosahexaenoic acid (DHA) on the inflammatory response and TREM2-dependent phagocytic activity in microglia was investigated.</p><p><strong>Methods: </strong>In LPS-induced primary microglia preincubated with DHA, or without preincubation the expression of ATF3 and TREM2 genes and TREM2, Syk, Akt proteins were determined by RT-PCR and WB, respectively. Cell viability was assayed by MTT and cytokine and chemokine expression was determined by the Proteome Profiler assay. Moreover, the phagocytic activity of microglia was assayed using immunofluorescence.</p><p><strong>Results: </strong>We found that DHA significantly increased the expression of ATF3 , and decreased the levels of CINC-1, CINC-2αβ, CINC-3 chemokines, IL-1α and IL-1β cytokines, and ICAM-1 adhesion protein. Additionally, preincubation of microglia with DHA resulted in increased Src/Syk kinases activation associated with increased phagocytic microglia activity.</p><p><strong>Conclusion: </strong>These findings indicate that DHA efficiently inhibits ATF3-dependent release of proinflammatory mediators and enhances phagocytic activity of microglia. The study provides a new mechanism of DHA action in reactive microglia, which may help limit neuronal damage caused by the pro-inflammatory milieu in the brain.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 6","pages":"411-425"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152958","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}
Suppressor of Ty homolog-5 (SPT5) discovered in the yeast mutant screens as a suppressor of mutation caused by the insertion of the Transposons of yeast (Ty) element along with SPT4, with which it forms a holoenzyme complex known as DRB sensitivity-inducing factor (DSIF) and plays an essential role in the regulation of transcription. SPT5 is a highly conserved protein across all three domains of life and performs critical functions in transcription, starting from promoter-proximal pausing to termination. We also highlight the emerging role of SPT5 in other non-canonical functions, such as the regulation of post-translational modifications (PTM) and the transcriptional regulation of non-coding genes. Also, in brief, we highlight the clinical implications of SPT5 dysregulation.
{"title":"Emerging Roles of SPT5 in Transcription.","authors":"Vivek Pandey, Shirani Punniyamoorthy, Yuba Raj Pokharel","doi":"10.33594/000000665","DOIUrl":"10.33594/000000665","url":null,"abstract":"<p><p>Suppressor of Ty homolog-5 (SPT5) discovered in the yeast mutant screens as a suppressor of mutation caused by the insertion of the Transposons of yeast (Ty) element along with SPT4, with which it forms a holoenzyme complex known as DRB sensitivity-inducing factor (DSIF) and plays an essential role in the regulation of transcription. SPT5 is a highly conserved protein across all three domains of life and performs critical functions in transcription, starting from promoter-proximal pausing to termination. We also highlight the emerging role of SPT5 in other non-canonical functions, such as the regulation of post-translational modifications (PTM) and the transcriptional regulation of non-coding genes. Also, in brief, we highlight the clinical implications of SPT5 dysregulation.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 5","pages":"395-408"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50157165","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}