General Information of the m6A Target Gene (ID: M6ATAR00682)
Target Name Target of rapamycin complex subunit LST8 (MLST8)
Synonyms
TORC subunit LST8; G protein beta subunit-like; Gable; Protein GbetaL; Mammalian lethal with SEC13 protein 8; mLST8
    Click to Show/Hide
Gene Name MLST8
Chromosomal Location 16p13.3
Family WD repeat LST8 family
Function
Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.
    Click to Show/Hide
Gene ID 64223
Uniprot ID
LST8_HUMAN
HGNC ID
HGNC:24825
Ensembl Gene ID
ENSG00000167965
KEGG ID
hsa:64223
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
MLST8 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
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line NOMO-1 cell line Homo sapiens
Treatment: shALKBH5 NOMO-1 cells
Control: shNS NOMO-1 cells
GSE144968
Regulation
logFC: -6.36E-01
p-value: 6.23E-04
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease.
Target Regulation Up regulation
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
Cell Process Cell apoptosis
In-vitro Model MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model HL-60 cells (1 × 107) suspended in 0.1 ml PBS containing 50% Matrigel were subcutaneously injected into the flanks of the mice. When tumor sizes reached 200 mm3, the mice were randomly distributed into four groups with the indicated dosages of saline, cytarabine and BP alone or in combination. For BP injections, the solution was delivered intraperitoneally at 106 ug/kg body weight for the first 8 consecutive days. For cytarabine injections, the solution was delivered intraperitoneally at 100 mg/kg body weight three times (once every three days). The combination group was administered intraperitoneally three times (once every three days) with the same dosages as described above. The control group was treated with an equivalent amount of saline.
Acute myeloid leukaemia [ICD-11: 2A60]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Bioactive peptides can inhibit acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and Target of rapamycin complex subunit LST8 (MLST8) mRNAs, which have potential to prevent and treat this disease.
Responsed Disease Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Cell Process Cell apoptosis
In-vitro Model MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model HL-60 cells (1 × 107) suspended in 0.1 ml PBS containing 50% Matrigel were subcutaneously injected into the flanks of the mice. When tumor sizes reached 200 mm3, the mice were randomly distributed into four groups with the indicated dosages of saline, cytarabine and BP alone or in combination. For BP injections, the solution was delivered intraperitoneally at 106 ug/kg body weight for the first 8 consecutive days. For cytarabine injections, the solution was delivered intraperitoneally at 100 mg/kg body weight three times (once every three days). The combination group was administered intraperitoneally three times (once every three days) with the same dosages as described above. The control group was treated with an equivalent amount of saline.
References
Ref 1 Bioactive peptide inhibits acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m(6)A demethylation of EIF4EBP1 and MLST8 mRNA. Cell Oncol (Dordr). 2022 Jun;45(3):355-365. doi: 10.1007/s13402-022-00666-9. Epub 2022 May 17.