STK4 x MST2

Last update 23 Jan 2025

Basic Info

Related Targets

STK4MST2

Drugs associated with STK4 x MST2

XMU-MP-1

Target

MST2 x STK4

Mechanism

MST2 modulators [+1]

Active Org.-

Originator Org.

Xiamen University

Active Indication-

Inactive Indication

Liver Injury

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with STK4 x MST2

100 Translational Medicine associated with STK4 x MST2

0 Patents (Medical) associated with STK4 x MST2

Literatures (Medical) associated with STK4 x MST2

17 Dec 2024·Medical Review

MST1 interactomes profiling across cell death in esophageal squamous cell carcinoma

Article

Author: Bi, Shanshan ; Wu, Yueguang ; Zhou, Yan ; Liu, Huijuan ; Cui, Yongping ; Gao, Mingwei ; Song, Qiqin ; Zhuang, Xuehan ; Zhang, Li ; Zhang, Weimin

AbstractObjectivesResistance to apoptosis in esophageal squamous cell carcinoma (ESCC) constitutes a significant impediment to treatment efficacy. Exploring alternative cell death pathways and their regulatory factors beyond apoptosis is crucial for overcoming drug resistance and enhancing therapeutic outcomes in ESCC.MethodsMammalian Ste 20-like kinase 1 (MST1) is implicated in regulating various cell deaths, including apoptosis, autophagy, and pyroptosis. Employing enhanced ascorbate peroxidase 2 (APEX2) proximity labeling coupled with immunoprecipitation-mass spectrometry (IP-MS), we elucidated the interactomes of MST1 across these three cell death paradigms.ResultsProteomic profiling unveiled the functional roles and subcellular localization of MST1 and its interacting proteins during normal proliferation and various cell death processes. Notably, MST1 exhibited an expanded interactome during cell death compared to normal proliferation and chromosome remodeling functions consistently. In apoptosis, there was a notable increase of mitosis-associated proteins such as INCENP, ANLN, KIF23, SHCBP1 and SUPT16H, which interacted with MST1, alongside decreased expression of the pre-apoptotic protein STK3. During autophagy, the bindings of DNA repair-related proteins CBX8 and m6A reader YTHDC1 to MST1 were enhanced. In pyroptosis, LRRFIP2 and FLII which can inhibit pyroptosis increasingly binding to MST1.ConclusionsOur findings delineate potential mechanisms through which MST1 and its interactomes regulate cell death, paving the way for further investigation to validate and consolidate these observations.

01 Jan 2024·Digestive Diseases

Association Study between SNPs in MST1 and MST2 and H. pylori Infection as well as Noncardia Gastric Carcinogenesis

Article

Author: Gao, Fang ; Jia, Yanbin ; Dong, Wenjie ; Ma, Licong ; Song, Qiang

Introduction: Gastric cancer (GC) remains a global health challenge, and H. pylori infection is a main risk factor for noncardia GC. The present study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in mammalian sterile 20-like kinase 1 (MST1) and MST2, H. pylori (H. pylori) infection, and the risk of noncardia gastric cancer (GC). Methods: A case-control study was conducted using enzyme-linked immunosorbent assay (ELISA) and TaqMan method to detect the titer of anti-H. pylori antibody in normal human serum and genotype 9 SNPs of MST1 and MST2 genes among 808 samples. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and H. pylori infection, as well as the risk of noncardia gastric cancer in codominant, dominant, overdominant, recessive, and log-additive genetic models. Haplotypes were constructed using the Haploview 4.2 software. Results: The CC genotype of MST2 SNP rs10955176 was associated with a reduced risk of H. pylori infection compared to the TT + CT genotype. None of other SNPs were associated with H. pylori infection. The TT genotype of MST2 SNP rs7827435 was associated with a reduced risk of noncardia gastric cancer compared to the AA + AT genotype. None of the SNPs were associated with noncardia gastric cancer. There were no associations between haplotypes and H. pylori infection or the risk of noncardia gastric cancer. Conclusions: The CC genotype of rs10955176 and the TT genotype of rs7827435 may serve as protective factors against H. pylori infection and noncardia gastric cancer risk, respectively.

01 Aug 2023·Allergy

Stk4, a key regulator in regulatory T cells homeostasis activity?

Author: Tomei, Leonardo ; Céspedes, Jose Antonio

A review.Regulatory T cells (Tregs) play an essential role modulating immune response through the surface marker expression and mediators′ release.Dysregulation in Treg numbers or dysfunction associated with allergy and autoimmune and inflammatory disorders development.Since the deficit of Stk4 has been associated with an increase in infections, autoimmunity, and immune dysregulation, its potential role modulating the activity of Tregs seems clear, although the concrete mechanism remains elusive.In this work, nine Stk4- deficient patients had atopic dermatitis, recurrent pneumonia, and cutaneous viral infections.Cui et al. In their work, Stk3/4-deficient mouse model showed a severe inflammation, with decreased Tregs numbers, expansion of effector memory T cell, and dysregulated interferon-γ (IFN-γ) expression.Concerning the stabilization complex by phosphorylation, Ye Cui et al. studied the colocation of FoxP3 with Stk4/p65 complex in Tregs with phosphomimetic residue in comparison to a phosphorylation-resistant cell, and the first one was more associated with the Stk4/ p65 complex than the resistant one.However, it is not entirely clear if Stk4 stabilizes Stk4-Foxp3-p65 complex formation.Patients with different loss-of-function mutations in Stk4 suffered a decrease in naive and central memory Tregs populations and an increase in effector Tregs populations without affecting the number of Tregs.Even though this article showed the potential role of Stk4 as regulatory activity of Tregs, more research is needed, as it was focused on a mouse model, and only in five patients.Furthermore, it is not completely clear how Stk4, but not Stk3, have a role controlling their activity.

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