scholarly journals Post-translational modifications regulate the activity of the growth restricting protease DA1

2021 ◽  
Author(s):  
Ying Chen ◽  
Dirk Inzé ◽  
Hannes Vanhaeren
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Organ Size ◽  
Negative Regulator ◽  
Renewable Energy Resources ◽  
Final Size ◽  
Post Translational Modifications ◽  
Important Trait ◽  
Multicellular Organisms ◽  
Fine Tune

Abstract Because plants are a primary food source and can form the basis for renewable energy resources, the final size of their organs is by far the most important trait to tackle when seeking increased plant productivity. Being multicellular organisms, plant organ size is mainly determined by the coordination between cell proliferation and cell expansion. The protease DA1 limits the duration of cell proliferation and hereby restricts final organ size. Since its initial identification as a negative regulator of organ growth, various transcriptional regulators of DA1, but also interacting proteins, have been identified. These interactors include cleavage substrates of DA1, but also proteins that modulate the activity of DA1 through post-translational modifications, such as ubiquitination, deubiquitination and phosphorylation. In addition, many players in the DA1 pathway display conserved phenotypes in other dicot and even monocot species. In this review, we give a timely overview of the complex, but intriguing molecular mechanisms that fine-tune the activity of DA1 and therefore final organ size, and we lay out a roadmap to identify and characterize substrates of proteases and frame the substrate cleavage events in their biological context.

scholarly journals TRIM22 activates NF-κB signaling in glioblastoma by accelerating the degradation of IκBα

2020 ◽  
Vol 28 (1) ◽  
pp. 367-381
Author(s):  
Jianxiong Ji ◽  
Kaikai Ding ◽  
Tao Luo ◽  
Xin Zhang ◽  
Anjing Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Active Sites ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Xenograft Model ◽  
E3 Ligase ◽  
Negative Regulator ◽  
Luciferase Reporter ◽  
Growth Promoting

AbstractNF-κB signaling plays a critical role in tumor growth and treatment resistance in GBM as in many other cancers. However, the molecular mechanisms underlying high, constitutive NF-κB activity in GBM remains to be elucidated. Here, we screened a panel of tripartite motif (TRIM) family proteins and identified TRIM22 as a potential activator of NF-κB using an NF-κB driven luciferase reporter construct in GBM cell lines. Knockout of TRIM22 using Cas9-sgRNAs led to reduced GBM cell proliferation, while TRIM22 overexpression enhanced proliferation of cell populations, in vitro and in an orthotopic xenograft model. However, two TRIM22 mutants, one with a critical RING-finger domain deletion and the other with amino acid changes at two active sites of RING E3 ligase (C15/18A), were both unable to promote GBM cell proliferation over controls, thus implicating E3 ligase activity in the growth-promoting properties of TRIM22. Co-immunoprecipitations demonstrated that TRIM22 bound a negative regulator of NF-κB, NF-κB inhibitor alpha (IκBα), and accelerated its degradation by inducing K48-linked ubiquitination. TRIM22 also formed a complex with the NF-κB upstream regulator IKKγ and promoted K63-linked ubiquitination, which led to the phosphorylation of both IKKα/β and IκBα. Expression of a non-phosphorylation mutant, srIκBα, inhibited the growth-promoting properties of TRIM22 in GBM cell lines. Finally, TRIM22 was increased in a cohort of primary GBM samples on a tissue microarray, and high expression of TRIM22 correlated with other clinical parameters associated with progressive gliomas, such as wild-type IDH1 status. In summary, our study revealed that TRIM22 activated NF-κB signaling through posttranslational modification of two critical regulators of NF-κB signaling in GBM cells.

scholarly journals Linker histone H1.5 is an underestimated factor in differentiation and carcinogenesis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Marthe Behrends ◽  
Olivia Engmann
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Mammalian Development ◽  
Research Attention ◽  
Post Translational Modifications ◽  
Linker Histones ◽  
The Family ◽  
Histone Modifying Enzymes ◽  
Fine Tune

Abstract Human histone H1.5, in mice called H1b, belongs to the family of linker histones (H1), which are key players in chromatin organization. These proteins sit on top of nucleosomes, in part to stabilize them, and recruit core histone modifying enzymes. Through subtype-specific deposition patterns and numerous post-translational modifications, they fine-tune gene expression and chromatin architecture, and help to control cell fate and homeostasis. However, even though it is increasingly implicated in mammalian development, H1.5 has not received as much research attention as its relatives. Recent studies have focused on its prognostic value in cancer patients and its contribution to tumorigenesis through specific molecular mechanisms. However, many functions of H1.5 are still poorly understood. In this review, we will summarize what is currently known about H1.5 and its function in cell differentiation and carcinogenesis. We will suggest key experiments that are required to understand the molecular network, in which H1.5 is embedded. These experiments will advance our understanding of the epigenetic reprogramming occurring in developmental and carcinogenic processes.

scholarly journals Integrative Roles of Phytohormones on Cell Proliferation, Elongation and Differentiation in the Arabidopsis thaliana Primary Root

2021 ◽  
Vol 12 ◽  
Author(s):  
Estephania Zluhan-Martínez ◽  
Brenda Anabel López-Ruíz ◽  
Mónica L. García-Gómez ◽  
Berenice García-Ponce ◽  
María de la Paz Sánchez ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Arabidopsis Thaliana ◽  
Molecular Mechanisms ◽  
Primary Root ◽  
Longitudinal Axis ◽  
Growth Responses ◽  
Root Cells ◽  
Multicellular Organisms ◽  
External Stimuli

The growth of multicellular organisms relies on cell proliferation, elongation and differentiation that are tightly regulated throughout development by internal and external stimuli. The plasticity of a growth response largely depends on the capacity of the organism to adjust the ratio between cell proliferation and cell differentiation. The primary root of Arabidopsis thaliana offers many advantages toward understanding growth homeostasis as root cells are continuously produced and move from cell proliferation to elongation and differentiation that are processes spatially separated and could be studied along the longitudinal axis. Hormones fine tune plant growth responses and a huge amount of information has been recently generated on the role of these compounds in Arabidopsis primary root development. In this review, we summarized the participation of nine hormones in the regulation of the different zones and domains of the Arabidopsis primary root. In some cases, we found synergism between hormones that function either positively or negatively in proliferation, elongation or differentiation. Intriguingly, there are other cases where the interaction between hormones exhibits unexpected results. Future analysis on the molecular mechanisms underlying crosstalk hormone action in specific zones and domains will unravel their coordination over PR development.

scholarly journals Decreased INPP5B Expression Predicts Poor Prognosis in Lung Adenocarcinoma

2021 ◽  
Author(s):  
jun deng ◽  
Xu Lin ◽  
Qi Li ◽  
Xiao-yu Cai ◽  
Lin-wen Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Prognostic Biomarker ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Negative Regulator ◽  
Ppi Network ◽  
Operating Characteristics ◽  
Cox Regression Analysis

Abstract Background Inositol Polyphosphate-5-Phosphatase B (INPP5B), ainositol 5-phosphatase, plays important roles in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential value of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD. Methods TCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic value of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses.The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction(PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays. Result INPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And low expression of INPP5B was associated with adverse-pathology features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for patients with LUAD. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the acitivity of PI3K/Akt signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the Akt pathway. Conclusion Our results demonstrated that INPP5Bcould inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for patients with LUAD. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People’s Hospital. The Ethics Committee of Hangzhou First People's Hospital have approved this study. (registration number:ⅡT-20210907-0031-01；registration date:2021.09.13)

scholarly journals The F-box protein MIO1/SLB1 regulates organ size and leaf movement in Medicago truncatula

2021 ◽  
Author(s):  
Shaoli Zhou ◽  
Tianquan Yang ◽  
Yawen Mao ◽  
Ye Liu ◽  
Shiqi Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Size Control ◽  
Organ Size ◽  
Primary Cell ◽  
Leaf Movement ◽  
Loss Of Function ◽  
Cellular Analysis ◽  
Final Yield ◽  
F Box Protein

Abstract The size of leaf and seed organs, determined by the interplay of cell proliferation and expansion, is closely related to the final yield and quality of forage and crops. Yet the cellular and molecular mechanisms underlying organ size modulation remain poorly understood, especially in legumes. Here, MINI ORGAN1 (MIO1) was identified as a key regulator of organ size, which encodes an F-box protein (SLB1) was recently reported to control lateral branching in M. truncatula. We show that loss of function of MIO1/SLB1 severely reduced organ size. Conversely, plants with overexpression of MIO1/SLB1 plants had enlarged organs. Cellular analysis revealed that MIO1/SLB1 controlled organ size mainly by modulating primary cell proliferation during the early stages of leaf development. Biochemistry analysis revealed MIO1/SLB1 could form part of an SKP1/Cullin/F-box (SCF) E3 ubiquitin ligase complex, to target BIG SEEDS1 (BS1), a repressor of primary cell division for degradation. Interestingly, we found that MIO1/SLB1 also played a key role in pulvinus development and leaf movement by modulating cell proliferation of the pulvinus as leaves developed. Our study not only demonstrates a conserved role of MIO1/SLB1 for organ size control in legumes, but also sheds light on the novel function of MIO1/SLB1 in leaf movement.

Inhibition of Migration and Invasion of Hepatocarcinoma HepG2 Cells by Dietary Saponins via Targeting HIF-1α

2018 ◽  
Vol 18 (7) ◽  
pp. 1025-1031
Author(s):  
Cheng Luo ◽  
Di Wu ◽  
Meiling Chen ◽  
Wenhua Miao ◽  
Changfeng Xue ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Confocal Microscopy ◽  
Protein Expression ◽  
Mtt Assay ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Rt Pcr ◽  
Gene And Protein Expression ◽  
Simulated Hypoxia

Background: Different saponins from herbs have been used as tonic or functional foods, and for treatment of various diseases including cancers. Although clinical data has supported the function of these saponins, their underlying molecular mechanisms have not been well defined. Methods: With the simulated hypoxia created by 8 hours of Cu++ exposure and following 24 hour incubation with different concentration of saponins in HepG2 cells for MTT assay, migration and invasion assays, and for RT-PCR, and with each group of cells for immunofluorescence observation by confocal microscopy. Results： ZC-4 had the highest rate of inhibition of cell proliferation by MTT assay, and the highest inhibition of migration rate by in vitro scratch assay, while ZC-3 had the highest inhibition of invasion ratio by transwell assay. Under the same simulated hypoxia, the molecular mechanism of saponin function was conducted by measuring the gene expression of Hypoxia Inducible Factor (HIF)-1α through RT-PCR, in which ZC-3 showed a potent inhibition of gene HIF-1α. For the protein expression by immunofluorescence staining with confocal microscopy, HIF-1α was also inhibited by saponins, with the most potent one being ZC-4 after eight hours’ relatively hypoxia incubation. Conclusion: Saponins ZC-4 and ZC-3 have the potential to reduce HepG2 cell proliferation, migration and invasion caused by hypoxia through effectively inhibiting the gene and protein expression of HIF-1α directly and as antioxidant indirectly

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals Expression and function of Smad7 in autoimmune and inflammatory diseases

2021 ◽  
Author(s):  
Yiping Hu ◽  
Juan He ◽  
Lianhua He ◽  
Bihua Xu ◽  
Qingwen Wang
Keyword(s):  
Posttranscriptional Regulation ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Signaling Mechanism ◽  
And Function

AbstractTransforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.

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