Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation

Wang, Chao; Chen, Zhe; Nie, Litong; Tang, Mengfan; Feng, Xu; Su, Dan; Zhang, Huimin; Xiong, Yun; Park, Jeong Min; Chen, Junjie

doi:10.1038/s41389-020-00271-1

Cited by 6 publications

(3 citation statements)

References 43 publications

(80 reference statements)

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“…Various stimuli such as cytokines, viruses, G-protein-bound receptor ligands and oncogenes play a regulatory role by activating the ERK/MAPK signalling pathway 64,65 . The ERK/MAPK signal pathway can be activated in the following ways: 1) Ca 2+ channel activation; 2) activation of Ras tyrosine kinase receptors; 3) PKC-mediated activation; 4) activation of receptors bound to G proteins 39,66 .…”

Section: Ras/raf/mek/erk Signal Cascadementioning

confidence: 99%

Cancer - dysregulation of the cell cycle and transduction of cascade signals

Akhmad

Khasanov

Abdurakhmonov

et al. 2021

Romanian Journal of Rhinology

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According to scientific data, cancer is a very ancient disease, and along with the perfection of humanity it becomes more progressive. The development of technologies that detect molecular changes in the pathogenesis and subsequent development of carcinogenesis has led to the beginning of a new era in oncology. The cell cycle is tightly controlled by a group of protein kinases, including cyclin and cyclin-dependent kinases. These events occur in a strictly regulated time sequence supported by consistent restriction points. p53, p21, p16, retinoblastoma (and other proteins), cyclins and cyclin-related kinases repair DNA before the cell cycle enters the phase of synthesis and mitosis. Loss of regulatory activity of p53 and pRB, stable activation of E2F stimulates uncontrolled cell proliferation, leading to neoplastic cell growth. The Ras/Raf/MEK/ERK signalling pathway is also a complex network of sequentially activated proteins that play a major role in the onset and development of cancer. It can regulate not only the biological functions, such as cell proliferation, cycle regulation, cell differentiation, apoptosis and tissue formation, but it is also associated with tumor development. Stable mutations in the genome or defects in the epigenome lead to dysregulation in the normal biological cycle of the cell, underlying DNA chain damage or dysfunction in the control system, determined by various types of carcinogenic factors, both known and unknown.

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Section: Ras/raf/mek/erk Signal Cascadementioning

confidence: 99%

Cancer - dysregulation of the cell cycle and transduction of cascade signals

Akhmad

Khasanov

Abdurakhmonov

et al. 2021

Romanian Journal of Rhinology

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“…For instance, polyamines, particularly spermidine, are required for the hypusination of the eukaryotic initiation factor 5A (eIF5A). Both of spermidine and hyp-eIF5A have been found upregulated in multiple types of cancers [ 12 – 15 ]. Hypusination is a unique post-translational modification, where the spermidine is added to eIF5A.…”

Section: Introductionmentioning

confidence: 99%

Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection

Fiches

Zhou

et al. 2022

PLoS Pathog

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Polyamines are critical metabolites involved in various cellular processes and often dysregulated in cancers. Kaposi’s sarcoma-associated Herpesvirus (KSHV), a defined human oncogenic virus, leads to profound alterations of host metabolic landscape to favor development of KSHV-associated malignancies. In our studies, we identified that polyamine biosynthesis and eIF5A hypusination are dynamically regulated by KSHV infection through modulation of key enzymes (ODC1 and DHPS) of these pathways. During KSHV latency, ODC1 and DHPS are upregulated along with increase of hypusinated eIF5A (hyp-eIF5A), while hyp-eIF5A is further induced along with reduction of ODC1 and intracellular polyamines during KSHV lytic reactivation. In return these metabolic pathways are required for both KSHV lytic reactivation and de novo infection. Further analysis unraveled that synthesis of critical KSHV latent and lytic proteins (LANA, RTA) depends on hypusinated-eIF5A. We also demonstrated that KSHV infection can be efficiently and specifically suppressed by inhibitors targeting these pathways. Collectively, our results illustrated that the dynamic and profound interaction of a DNA tumor virus (KSHV) with host polyamine biosynthesis and eIF5A hypusination pathways promote viral propagation, thus defining new therapeutic targets to treat KSHV-associated malignancies.

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“…In vitro, HOMER1 promoted the proliferation, migration, and invasion of colorectal cancer cells by upregulating G3BP1 (Cui, et al, 2020). ERK-mediated Ser-233 phosphorylation of DHPS can affect cell proliferation, and high expression of DHPS was associated with poor prognosis of lung adenocarcinoma (Wang, et al, 2020). According to Kai-Li Liu et al, DHPS inhibitors inhibited the invasion and migration of melanoma cells (Liu, et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

T cell proliferation-related genes: Predicting prognosis, identifying the cold and hot tumors, and guiding treatment in clear cell renal cell carcinoma

et al. 2022

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Background: Immunotherapy has become a new direction of current research because the effect of traditional radiotherapy and chemotherapy on clear cell renal cell carcinoma (ccRCC) is not satisfactory. T cell proliferation-related genes (TRGs) play a pivotal role in tumor progression by regulating the proliferation, activity, and function of immune cells. The purpose of our study is to construct and verify a prognostic model based on TRGs and to identify tumor subtypes that may guide treatment through comprehensive bioinformatics analyses.Methods: RNA sequencing data, clinical information, and somatic mutation data of ccRCC are obtained from The Cancer Genome Atlas (TCGA) database. We identified the prognosis-related TRGs which were differentially expressed between normal and tumor tissues. After dividing the patients into a train set and a test set according to proportion 1:1 randomly, the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were performed to construct a risk-stratified model. Its prediction performance was verified. Then, Gene Set Enrichment Analysis (GSEA), principal component analysis (PCA), tumor microenvironment (TME) analysis, and the half-maximal inhibitory concentration (IC50) prediction were performed between the different groups of patients. To further discuss the immunotherapy between hot and cold tumors, we divided all patients into two clusters based on TRGs through unsupervised learning. Analyzing the gene mutation and calculating the tumor mutation burden (TMB), we further explored the relationship between somatic mutations and grouping or clustering.Results: Risk-stratified model and nomogram predict the prognosis of ccRCC patients accurately. Functional enrichment analyses suggested that TRGs mainly focused on the biological pathways related to tumor progression and immune response. Different tumor microenvironment, drug resistance, and TMB can be distinguished clearly according to both risk stratification and tumor subtype clustering.Conclusion: In this study, a new stratification model of ccRCC based on TRGs was established, which can accurately predict the prognosis of patients. IC50 prediction may guide the application of anti-tumor drugs. The distinction between hot and cold tumors provides a reference for clinical immunotherapy.

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Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation

Cited by 6 publications

References 43 publications

Cancer - dysregulation of the cell cycle and transduction of cascade signals

Cancer - dysregulation of the cell cycle and transduction of cascade signals

Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection

T cell proliferation-related genes: Predicting prognosis, identifying the cold and hot tumors, and guiding treatment in clear cell renal cell carcinoma

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