General Information of the m6A Target Gene (ID: M6ATAR00327)
Target Name Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1)
Synonyms
MAP kinase 1; MAPK 1; ERT1; Extracellular signal-regulated kinase 2; ERK-2; MAP kinase isoform p42; p42-MAPK; Mitogen-activated protein kinase 2; MAP kinase 2; MAPK 2; ERK2; PRKM1; PRKM2
    Click to Show/Hide
Gene Name MAPK1
Chromosomal Location 22q11.22
Family protein kinase superfamily; CMGC Ser/Thr protein kinase family; MAP kinase subfamily
Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). ; Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
    Click to Show/Hide
Gene ID 5594
Uniprot ID
MK01_HUMAN
HGNC ID
HGNC:6871
Ensembl Gene ID
ENSG00000100030
KEGG ID
hsa:5594
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
MAPK1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Browse Drug
Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) [READER]
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary hnRNPA2B1 promotes colon cancer progression via the MAPK pathway. hnRNPA2B1 is an upstream regulator of the ERK/Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1.
Target Regulation Up regulation
Responsed Disease Colon cancer ICD-11: 2B90
Pathway Response MAPK signaling hsa04010
Cell Process Arrest cell cycle at G0/G1 phase
Cell apoptosis
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
In-vivo Model Four-week-old male BALB/c nude mice (purchased from Lingchang company) were randomly divided into three groups, each group has five mice. Each of the mice was injected subcutaneously on the right lateral back with 1 × 106 of each lentivirus infected SW480 cells in which hnRNPA2B1 was knocked out or negative control cells. Mice were killed at day 29, and tumors were then isolated, photographed.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant- resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
Responsed Drug Fulvestrant Approved
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
Responsed Drug Tamoxifen Approved
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) [READER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1), AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Target Regulation Up regulation
Responsed Disease Gangrene or necrosis of lung ICD-11: CA43
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
YTH domain-containing family protein 3 (YTHDF3) [READER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1), AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Target Regulation Up regulation
Responsed Disease Gangrene or necrosis of lung ICD-11: CA43
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
Colon cancer [ICD-11: 2B90]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary hnRNPA2B1 promotes colon cancer progression via the MAPK pathway. hnRNPA2B1 is an upstream regulator of the ERK/Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1.
Responsed Disease Colon cancer [ICD-11: 2B90]
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
Target Regulation Up regulation
Pathway Response MAPK signaling hsa04010
Cell Process Arrest cell cycle at G0/G1 phase
Cell apoptosis
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
In-vivo Model Four-week-old male BALB/c nude mice (purchased from Lingchang company) were randomly divided into three groups, each group has five mice. Each of the mice was injected subcutaneously on the right lateral back with 1 × 106 of each lentivirus infected SW480 cells in which hnRNPA2B1 was knocked out or negative control cells. Mice were killed at day 29, and tumors were then isolated, photographed.
Colorectal cancer [ICD-11: 2B91]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of colorectal cancer. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1), EGFR, and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these "writers" to aid the clinical benefits of immunotherapy.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Pathway Response MAPK signaling pathway hsa04010
VEGF signaling pathway hsa04370
mTOR signaling pathway hsa04150
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Apoptosis hsa04210
Cell Process Cell apoptosis
Breast cancer [ICD-11: 2C60]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant- resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
Target Regulation Up regulation
Responsed Drug Fulvestrant Approved
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
Target Regulation Up regulation
Responsed Drug Tamoxifen Approved
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Gangrene or necrosis of lung [ICD-11: CA43]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1), AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Responsed Disease Gangrene or necrosis of lung [ICD-11: CA43]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1), AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and TNF-alpha secretion.
Responsed Disease Gangrene or necrosis of lung [ICD-11: CA43]
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
Fulvestrant [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant- resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
Tamoxifen [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary In breast cancer, modest stable overexpression of A2B1 in MCF-7 cells (MCF-7-A2B1 cells) resulted in tamoxifen and fulvestrant - resistance whereas knockdown of A2B1 in LCC9 and LY2 cells restored tamoxifen and fulvestrant, endocrine-sensitivity. MCF-7-A2B1 cells have increased ER-alpha and reduced miR-222-3p that targets ER-alpha. MCF-7-A2B1 have activated AKT and Mitogen-activated protein kinase 1 (MAPK/ERK2/MAPK1) that depend on A2B1 expression and are growth inhibited by inhibitors of these pathways.
Target Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Cell Process Cell migration and invasion
In-vitro Model HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
References
Ref 1 hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway. Front Genet. 2021 Sep 22;12:666451. doi: 10.3389/fgene.2021.666451. eCollection 2021.
Ref 2 HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells. Cancer Lett. 2021 Oct 10;518:152-168. doi: 10.1016/j.canlet.2021.07.015. Epub 2021 Jul 14.
Ref 3 N6-methyladenosine reader YTH N6-methyladenosine RNA binding protein 3 or insulin like growth factor 2 mRNA binding protein 2 knockdown protects human bronchial epithelial cells from hypoxia/reoxygenation injury by inactivating p38 MAPK, AKT, ERK1/2, and NF-KappaB pathways. Bioengineered. 2022 May;13(5):11973-11986. doi: 10.1080/21655979.2021.1999550.