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Last update 08 May 2025

APBA3

Last update 08 May 2025

Basic Info

Synonyms

Adapter protein X11gamma, amyloid beta precursor protein binding family A member 3, Amyloid-beta A4 precursor protein-binding family A member 3

+ [6]

Introduction

May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. May enhance the activity of HIF1A in macrophages by inhibiting the activity of HIF1AN.

Drugs associated with APBA3

Naphthofluorescein

Target

APBA3

Mechanism

APBA3 inhibitors

Active Org.

Kanazawa Graduate School of Medicine

Originator Org.

Kanazawa Graduate School of Medicine

Active Indication

Hepatocellular Carcinoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with APBA3

100 Translational Medicine associated with APBA3

0 Patents (Medical) associated with APBA3

Literatures (Medical) associated with APBA3

01 Aug 2025·Cellular Signalling

MINT3 promotes STING activation and facilitates antiviral immune responses

Article

Author: Kong, Hongyi ; Zhao, Wei ; Shi, Tongrui ; Jia, Mutian ; Wang, Caiwei ; Sun, Wenyue ; Fu, Yue ; Liang, Wenbo ; Song, Hui ; Li, Qizhao

Stimulator-of-interferon genes (STING) translocation is the rate-limiting step in the cGAS-STING signaling which detects cytosolic DNA and produces type I interferons. However, the mechanism by which this process is modulated remains to be further clarified. In the present study, we identified munc18-1-interacting protein 3 (MINT3) as a positive regulator of STING signaling. MINT3 promotes type I interferons (IFN-I) production induced by herpes simplex virus-1 (HSV-1) infection and ISD or cGAMP stimulation in mouse peritoneal macrophages. Deficiency of Mint3 greatly inhibited STING and IRF3 activation in macrophages. Mint3 knockdown also attenuated STING and IRF3 activation in macrophages, human THP-1 cells, and RAW264.7 cells. Mechanistically, MINT3 interacted with STING, selectively enhanced its K63-linked polyubiquitination and facilitated STING translocation to the Golgi, resulting in the enhancement of the STING and TBK1 interaction. Furthermore, MINT3 also facilitated HSV-1-induced innate antiviral immune responses and impaired HSV-1 replication in vitro and in vivo. Interestingly, we showed that the expression of MINT3 was dramatically elevated during HSV-1 infection, and ISD stimulation in macrophages. Thus, we have revealed a feedback mechanism for the regulation of the cGAS-STING pathway, providing a promising therapeutic target for the treatment of disorders triggered by aberrant STING activity.

31 Aug 2023·Cells

MT1-MMP as a Key Regulator of Metastasis.

Review

Author: Sakamoto, Takeharu ; Tanaka, Noritaka

Membrane type1-matrix metalloproteinase (MT1-MMP) is a member of metalloproteinases that is tethered to the transmembrane. Its major function in cancer progression is to directly degrade the extracellular matrix components, which are mainly type I-III collagen or indirectly type IV collagen through the activation of MMP-2 with a cooperative function of the tissue inhibitor of metalloproteinase-2 (TIMP-2). MT1-MMP is expressed as an inactive form (zymogen) within the endoplasmic reticulum (ER) and receives truncation processing via furin for its activation. Upon the appropriate trafficking of MT1-MMP from the ER, the Golgi apparatus to the cell surface membrane, MT1-MMP exhibits proteolytic activities to the surrounding molecules such as extracellular matrix components and cell surface molecules. MT1-MMP also retains a non-proteolytic ability to activate hypoxia-inducible factor 1 alpha (HIF-1A) via factors inhibiting the HIF-1 (FIH-1)-Mint3-HIF-1 axis, resulting in the upregulation of glucose metabolism and oxygen-independent ATP production. Through various functions of MT1-MMP, cancer cells gain motility on migration/invasion, thus causing metastasis. Despite the long-time efforts spent on the development of MT1-MMP interventions, none have been accomplished yet due to the side effects caused by off-target effects. Recently, MT1-MMP-specific small molecule inhibitors or an antibody have been reported and these inhibitors could potentially be novel agents for cancer treatment.

01 Nov 2021·Journal of Biological ChemistryQ2 · BIOLOGY

Structural and thermodynamical insights into the binding and inhibition of FIH-1 by the N-terminal disordered region of Mint3

Q2 · BIOLOGY

Article

Author: Tensho Ten ; Ryo Maeda ; Motoharu Seiki ; Kouhei Tsumoto ; Takeharu Sakamoto ; Masaru Hoshino ; Yoshiaki Nakayama ; Satoru Nagatoishi

Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which makes investigation of this interaction challenging. Therefore, we adopted thermodynamic and structural studies in solution to clarify the structural and thermodynamical changes of Mint3 binding to FIH-1. First, using a combination of circular dichroism, nuclear magnetic resonance, and hydrogen/deuterium exchange-mass spectrometry (HDX-MS), we confirmed that the N-terminal half, which is the interacting part of Mint3, is mostly disordered. Next, we revealed a large enthalpy and entropy change in the interaction of Mint3 using isothermal titration calorimetry (ITC). The profile is consistent with the model that the flexibility of disordered Mint3 is drastically reduced upon binding to FIH-1. Moreover, we performed a series of ITC experiments with several types of truncated Mint3s, an effective approach since the interacting part of Mint3 is disordered, and identified amino acids 78 to 88 as a novel core site for binding to FIH-1. The truncation study of Mint3 also revealed the thermodynamic contribution of each part of Mint3 to the interaction with FIH-1, where the core sites contribute to the affinity (ΔG), while other sites only affect enthalpy (ΔH), by forming noncovalent bonds. This insight can serve as a foothold for further investigation of intrinsically disordered regions (IDRs) and drug development for cancer therapy.

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APBA3

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