MAPK4

Last update 08 May 2025

Basic Info

Synonyms

ERK-4, Erk3-related, ERK4

+ [8]

Introduction

Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity).

100 Clinical Results associated with MAPK4

100 Translational Medicine associated with MAPK4

0 Patents (Medical) associated with MAPK4

182

Literatures (Medical) associated with MAPK4

01 May 2025·Molecular Neurobiology

Microcystin-LR Exposure Damages Neurons by Inducing α-Syn Aggregation via MAPK4/GATA2/SNCA and PP2A/GRKs Pathways

Article

Author: Su, Chengxiang ; Wu, Huifang ; Wu, Tong ; Li, Dongmei ; Han, Xiaodong ; Wang, Yuhan ; Yan, Minghao

Microcystin-LR (MC-LR) is a natural neurotoxin with strong toxicity, and studies have demonstrated that chronic MC-LR exposure generated Parkinson-like dyskinesia in mice. Parkinson's disease (PD) is a neurologic degenerative disease mostly occurring in elderly people, and the progressive loss of dopaminergic neurons and the formation of Lewy bodies are the hallmark pathological features. The main component of Lewy bodies is α-synuclein (α-syn) encoded by the SNCA gene, and the copy number mutation of SNCA gene can promote the overexpression of α-syn. A mouse model of MC-LR exposure for 15 months was established to confirm the deposition of Lewy bodies. SH-SY5Y cells exposed to MC-LR were constructed as an in vitro model of PD, and the transcription factor that regulated the SNCA gene (the encoding gene of α-syn) was identified through the database. MC-LR enhanced the transcription level of SNCA gene and upregulated α-syn protein expression by promoting MAPK4 into the nucleus and binding to GATA2 295-480 fragment. In addition, MC-LR inhibited PP2A activity and activated GRKs kinase to promote α-syn phosphorylation at Ser129. These results suggest that MC-LR is involved in α-syn aggregate formation and PD pathogenesis by enhancing SNCA transcriptional activity to promote α-syn elevation via the MAPK4/GATA2 pathway and inducing α-syn phosphorylation via the PP2A/GRKs pathway.

06 Jan 2025·Journal of Pharmacy and Pharmacology

Anti-liver cancer therapeutic targets and safety of usenamine A in experimental liver cancer

Article

Author: Yao, Qian ; Wang, Jing ; Lian, Wenjing ; Zhou, Zhangping ; Zhao, Qing ; You, Yutong ; Fan, Shirui ; He, Xiaoqiong

AbstractBackgroundLiver cancer is highly heterogeneous with poor drug response. Usenamine A has anticancer activity. Usnic acid has hepatocytotoxicity.ObjectivesAs a derivative of usnic acid, if usenamine A can be safely used in treatment for liver cancer is unknown.MethodsMTT and clone formation assays assessed cell viability and proliferation. Tumor growth was determined using a xenograft model. Flow cytometry was used to detect the cell cycle. mRNA transcriptome sequencing investigated differential gene expression. Safety was evaluated in mice.Key findingsUsenamine A inhibited proliferation and clone formation of HepG2 cells and xenograft tumor growth through cell cycle arrest at G0/G1. Usenamine A altered gene expression in a direction supporting anticancer activity. IL24, JUN, DUSP4, and DUSP5 were upregulated while PRKACA, PRKCB, TP53, WNT6, E2F3, LGR4, GPR78, and MAPK4 were downregulated. Ten of above genes overlapped in the KEGG enriched non-small cell lung cancer/glioma/cytokine–cytokine receptor interaction/Wnt/MAPK pathway network. Usenamine A has a strong binding affinity for PRKACA and PRKCB proteins. Usenamine A showed minimal toxicity in mice.ConclusionsUsenamine A is a safe anticancer agent against hepatocellular carcinoma. Regulation of 12 cancer-associated genes and the correlated pathway network are its therapeutic targets.

01 Jan 2025·The International Journal of Biological Markers

Establishment of liquid–liquid phase separation-related prognostic model in lung adenocarcinoma and systematic analysis of its clinical significance

Article

Author: Chen, Yan ; Huang, Cheng ; Wei, Wei

PurposeTo detect the prognostic importance of liquid–liquid phase separation (LLPS) in lung adenocarcinoma.MethodsThe gene expression files, copy number variation data, and clinical data were downloaded from The Cancer Genome Atlas cohort. LLPS-related genes were acquired from the DrLLPS website. The prognostic model based on LLPS was constructed by the Cox regression and LASSO regression analyses after the identification of LLPS-related differentially expressed genes (DEGs). Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed. The LLPS-related prognostic risk score was validated by GSE31210 and GSE72094. The overall survival of lung adenocarcinoma patients was predicted by plotting a nomogram. The biological features of the high-risk lung adenocarcinoma were evaluated by the CIBERSORT, ESTIMATE, Gene Set Variation Analysis, and Genomics of Drug Sensitivity in Cancer. Reverse transcription-quantitative polymerase chain reaction detected hub gene expression.Results A total of 91 DEGs were screened out in LLPS, among which 9 genes were discovered as prognostic biomarkers of lung adenocarcinoma. GRIA1 , CRTAC1 , MAGEA4 , and MAPK4 were identified as hub genes by the LASSO Cox regression analysis. High-risk and low-risk groups were divided according to the risk index, with the high-risk group displaying a markedly worse outcome. CRTAC1 expression was significantly decreased, MAGEA4 and MAPK4 expressions were increased, while GRIA1 expression was altered in lung adenocarcinoma cells. Tumor microenvironment, signaling pathway enrichment, and drug sensitivity significantly differed between different risk groups. ConclusionsThis work proposed a prognostic tool based on the LLPS-related gene signature to offer prospective and effective biomarkers for lung adenocarcinoma prognosis.

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