Molecule Information
General Information of the Molecule (ID: Mol00657)
Name |
Serine/threonine-protein kinase 4 (MST1)
,Homo sapiens
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Synonyms |
Mammalian STE20-like protein kinase 1; MST-1; STE20-like kinase MST1; Serine/threonine-protein kinase Krs-2; MST1/N; MST1/C; KRS2; MST1
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Molecule Type |
Protein
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Gene Name |
STK4
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Gene ID | |||||
Location |
chr20:44966479-45080021[+]
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Sequence |
METVQLRNPPRRQLKKLDEDSLTKQPEEVFDVLEKLGEGSYGSVYKAIHKETGQIVAIKQ
VPVESDLQEIIKEISIMQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKT LTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAK RNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNP PPTFRKPELWSDNFTDFVKQCLVKSPEQRATATQLLQHPFVRSAKGVSILRDLINEAMDV KLKRQESQQREVDQDDEENSEEDEMDSGTMVRAVGDEMGTVRVASTMTDGANTMIEHDDT LPSQLGTMVINAEDEEEEGTMKRRDETMQPAKPSFLEYFEQKEKENQINSFGKSVPGPLK NSSDWKIPQDGDYEFLKSWTVEDLQKRLLALDPMMEQEIEEIRQKYQSKRQPILDAIEAK KRRQQNF Click to Show/Hide
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Function |
Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.
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Uniprot ID | |||||
Ensembl ID | |||||
HGNC ID | |||||
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Type(s) of Resistant Mechanism of This Molecule
UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
4 drug(s) in total
Cisplatin
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Ovarian cancer | [1] | |||
Resistant Disease | Ovarian cancer [ICD-11: 2C73.0] | |||
Resistant Drug | Cisplatin | |||
Molecule Alteration | Expression | Down-regulation |
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Experimental Note | Revealed Based on the Cell Line Data | |||
Cell Pathway Regulation | Cell apoptosis | Inhibition | hsa04210 | |
Hippo signaling pathway | Inhibition | hsa04390 | ||
In Vitro Model | SkOV3 cells | Ovary | Homo sapiens (Human) | CVCL_0532 |
A2780 cells | Ovary | Homo sapiens (Human) | CVCL_0134 | |
OVCAR3 cells | Ovary | Homo sapiens (Human) | CVCL_0465 | |
HO8910 cells | Ovary | Homo sapiens (Human) | CVCL_6868 | |
CAOV3 cells | Ovary | Homo sapiens (Human) | CVCL_0201 | |
ES-2 cells | Ovary | Homo sapiens (Human) | CVCL_3509 | |
TOV-21G cells | Ovary | Homo sapiens (Human) | CVCL_3613 | |
In Vivo Model | Nude mouse xenograft model | Mus musculus | ||
Experiment for Molecule Alteration |
Western blot analysis | |||
Experiment for Drug Resistance |
Flow cytometry assay | |||
Mechanism Description | miR-149-5p promotes the chemoresistance of ovarian cancer cells by directly targeting MST1 and SAV1, leading to the inactivation of Hippo signaling. |
Fluorouracil
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Pancreatic cancer | [2] | |||
Resistant Disease | Pancreatic cancer [ICD-11: 2C10.3] | |||
Resistant Drug | Fluorouracil | |||
Molecule Alteration | Expression | Down-regulation |
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Experimental Note | Revealed Based on the Cell Line Data | |||
Cell Pathway Regulation | Cell apoptosis | Inhibition | hsa04210 | |
Hippo signaling pathway | Regulation | hsa04392 | ||
In Vitro Model | BxPC-3 cells | Pancreas | Homo sapiens (Human) | CVCL_0186 |
PANC-1 cells | Pancreas | Homo sapiens (Human) | CVCL_0480 | |
Experiment for Molecule Alteration |
Western blot analysis | |||
Experiment for Drug Resistance |
Flow cytometry assay | |||
Mechanism Description | miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. |
Gemcitabine
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Pancreatic cancer | [2] | |||
Resistant Disease | Pancreatic cancer [ICD-11: 2C10.3] | |||
Resistant Drug | Gemcitabine | |||
Molecule Alteration | Expression | Down-regulation |
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Experimental Note | Revealed Based on the Cell Line Data | |||
Cell Pathway Regulation | Cell apoptosis | Inhibition | hsa04210 | |
Hippo signaling pathway | Regulation | hsa04392 | ||
In Vitro Model | BxPC-3 cells | Pancreas | Homo sapiens (Human) | CVCL_0186 |
PANC-1 cells | Pancreas | Homo sapiens (Human) | CVCL_0480 | |
Experiment for Molecule Alteration |
Western blot analysis | |||
Experiment for Drug Resistance |
Flow cytometry assay | |||
Mechanism Description | miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. |
Paclitaxel
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Pancreatic cancer | [2] | |||
Resistant Disease | Pancreatic cancer [ICD-11: 2C10.3] | |||
Resistant Drug | Paclitaxel | |||
Molecule Alteration | Expression | Down-regulation |
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Experimental Note | Revealed Based on the Cell Line Data | |||
Cell Pathway Regulation | Cell apoptosis | Inhibition | hsa04210 | |
Hippo signaling pathway | Regulation | hsa04392 | ||
In Vitro Model | BxPC-3 cells | Pancreas | Homo sapiens (Human) | CVCL_0186 |
PANC-1 cells | Pancreas | Homo sapiens (Human) | CVCL_0480 | |
Experiment for Molecule Alteration |
Western blot analysis | |||
Experiment for Drug Resistance |
Flow cytometry assay | |||
Mechanism Description | miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. |
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
Pancreatic cancer [ICD-11: 2C10]
Differential expression of molecule in resistant diseases | ||
The Studied Tissue | Pancreas | |
The Specified Disease | Pancreatic cancer | |
The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 7.18E-01; Fold-change: 4.31E-01; Z-score: 3.73E-01 | |
The Expression Level of Disease Section Compare with the Adjacent Tissue | p-value: 7.20E-03; Fold-change: 6.64E-01; Z-score: 6.32E-01 | |
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Ovarian cancer [ICD-11: 2C73]
Differential expression of molecule in resistant diseases | ||
The Studied Tissue | Ovary | |
The Specified Disease | Ovarian cancer | |
The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 3.44E-03; Fold-change: 3.70E-01; Z-score: 1.41E+00 | |
The Expression Level of Disease Section Compare with the Adjacent Tissue | p-value: 5.36E-03; Fold-change: -5.23E-01; Z-score: -1.00E+00 | |
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Tissue-specific Molecule Abundances in Healthy Individuals
References
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