General Information of the m6A Target Gene (ID: M6ATAR00313)
Target Name Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K)
Synonyms
S6K-beta-1; S6K1; 70 kDa ribosomal protein S6 kinase 1; P70S6K1; p70-S6K 1; Ribosomal protein S6 kinase I; Serine/threonine-protein kinase 14A; p70 ribosomal S6 kinase alpha; p70 S6 kinase alpha; p70 S6K-alpha; p70 S6KA; STK14A
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Gene Name RPS6KB1
Chromosomal Location 17q23.1
Family protein kinase superfamily; AGC Ser/Thr protein kinase family; S6 kinase subfamily
Function
Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition.
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Gene ID 6198
Uniprot ID
KS6B1_HUMAN
HGNC ID
HGNC:10436
Ensembl Gene ID
ENSG00000108443
KEGG ID
hsa:6198
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
RPS6KB1 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
Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line CT26 cell line Mus musculus
Treatment: METTL3 knockout CT26 cells
Control: CT26 cells
GSE142589
Regulation
logFC: -6.86E-01
p-value: 2.67E-02
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between RPS6KB1 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 1.70E+00 GSE60213
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K) and Cyclin D1.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 promotes the progression of retinoblastoma through PI3K/AKT/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K)/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.
Target Regulation Up regulation
Responsed Disease Retinoblastoma ICD-11: 2D02.2
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Cell Process Cell proliferation
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model WERI-Rb-1 Retinoblastoma Homo sapiens CVCL_1792
Y-79 Retinoblastoma Homo sapiens CVCL_1893
In-vivo Model To establish a subcutaneous tumour model in nude mice, 2 × 107 Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 106 per mouse).
Gastric cancer [ICD-11: 2B72]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K) and Cyclin D1.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Retina cancer [ICD-11: 2D02]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 promotes the progression of retinoblastoma through PI3K/AKT/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K)/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.
Responsed Disease Retinoblastoma [ICD-11: 2D02.2]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Cell Process Cell proliferation
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model WERI-Rb-1 Retinoblastoma Homo sapiens CVCL_1792
Y-79 Retinoblastoma Homo sapiens CVCL_1893
In-vivo Model To establish a subcutaneous tumour model in nude mice, 2 × 107 Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 106 per mouse).
References
Ref 1 METTL3 Promotes the Proliferation and Mobility of Gastric Cancer Cells. Open Med (Wars). 2019 Mar 2;14:25-31. doi: 10.1515/med-2019-0005. eCollection 2019.
Ref 2 m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway. J Cell Mol Med. 2020 Oct 8;24(21):12368-78. doi: 10.1111/jcmm.15736. Online ahead of print.