TBKBP1

Last update 08 May 2025

Basic Info

Synonyms

KIAA0775, ProSAPiP2, SINTBAD

+ [4]

Introduction

Adapter protein which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity.

100 Clinical Results associated with TBKBP1

100 Translational Medicine associated with TBKBP1

0 Patents (Medical) associated with TBKBP1

Literatures (Medical) associated with TBKBP1

01 Jan 2025·Traffic

Adaptor‐Mediated Trafficking of Tank Binding Kinase 1 During Diverse Cellular Processes

Review

Author: Paul, Swagatika ; Pickrell, Alicia M. ; Biswas, Sahitya Ranjan ; Milner, Julia P. ; Tomsick, Porter L.

ABSTRACTThe serine/threonine kinase, Tank Binding Kinase 1 (TBK1), drives distinct cellular processes like innate immune signaling, selective autophagy, and mitosis. It is suggested that the translocation and activation of TBK1 at different subcellular locations within the cell, downstream of diverse stimuli, are driven by TBK1 adaptor proteins forming a complex directly or indirectly with TBK1. Various TBK1 adaptors and associated proteins like NAP1, TANK, SINTBAD, p62, optineurin (OPTN), TAX1BP1, STING, and NDP52 have been identified in facilitating TBK1 activation and recruitment with varying overlapping redundancy. This review focuses on what is known about these proteins, their interactions with TBK1, and the functional consequences of these associations. We shed light on underexplored areas of research on these TBK1 binding partners while emphasizing how future research is required to understand the function and flexibility of TBK1 signaling and crosstalk or regulation between different biological processes.

01 Nov 2024·Nature Structural & Molecular Biology

Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD

Article

Author: Nguyen, Thanh Ngoc ; Khuu, Grace ; Shoebridge, Stephen ; Padman, Benjamin Scott ; Watts, Emily Maria ; Sawa-Makarska, Justyna ; Csalyi, Kitti Dora ; Martens, Sascha ; Adriaenssens, Elias ; Lazarou, Michael ; Skulsuppaisarn, Marvin ; Schuschnig, Martina

AbstractMitophagy preserves overall mitochondrial fitness by selectively targeting damaged mitochondria for degradation. The regulatory mechanisms that prevent PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase Parkin (PINK1/Parkin)-dependent mitophagy and other selective autophagy pathways from overreacting while ensuring swift progression once initiated are largely elusive. Here, we demonstrate how the TBK1 (TANK-binding kinase 1) adaptors NAP1 (NAK-associated protein 1) and SINTBAD (similar to NAP1 TBK1 adaptor) restrict the initiation of OPTN (optineurin)-driven mitophagy by competing with OPTN for TBK1. Conversely, they promote the progression of nuclear dot protein 52 (NDP52)-driven mitophagy by recruiting TBK1 to NDP52 and stabilizing its interaction with FIP200. Notably, OPTN emerges as the primary recruiter of TBK1 during mitophagy initiation, which in return boosts NDP52-mediated mitophagy. Our results thus define NAP1 and SINTBAD as cargo receptor rheostats, elevating the threshold for mitophagy initiation by OPTN while promoting the progression of the pathway once set in motion by supporting NDP52. These findings shed light on the cellular strategy to prevent pathway hyperactivity while still ensuring efficient progression.

01 Nov 2024·Drug Development Research

PARP7i Clinical Candidate RBN‐2397 Exerts Antiviral Activity by Modulating Interferon‐β Associated Innate Immune Response in Macrophages

Article

Author: Kang, Yanhua ; Du, Xiaoli ; Zhang, Hang ; Wang, Liwei ; Zhao, Dongjiu ; Chen, Yulong ; Zhou, Jiawei ; Xie, Tian ; Zhou, Yi ; Ye, Xiang‐Yang

ABSTRACTPolyadenosine diphosphate‐ribose polymerase 7 (PARP7) acts as a suppressor of the type I interferon (IFN) signaling pathway via suppressing TANK‐binding protein 1 (TBK1). Research study indicates that inhibition of PARP7 could potentially regulate tumor immunity. However, the effect of PARP7 inhibition on innate antiviral immunity in macrophages as well as the underlying mechanism have not been demonstrated else well. We report herein that PARP7 inhibitor clinical candidate RBN‐2397 could augment type I interferon (IFN‐I) production in macrophages by elevating retinoic acid‐inducible gene I (RIG‐I) and stimulator of interferon genes (STING) signaling pathways. Treatment with RBN‐2397 leads to increased pattern recognition ligands‐induced interferon‐β production in primary bone marrow‐derived macrophages (BMDM) and RAW264.7 cells. Additionally, RBN‐2397 suppresses viral replication efficiency in macrophages infected by vesicular stomatitis virus (VSV) and amplifies the expression of interferon‐stimulated chemokine genes (ISGs). Mechanistically, RBN‐2397 promotes TBK1 phosphorylation, consequently leading to the amplified activation of RIG‐I and STING signaling pathways. Furthermore, RBN‐2397 enhances the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2 induced by IFN‐α/β and the expression of chemokine genes in macrophages in response to IFN stimulation. In vivo experiments demonstrated that RBN‐2397 enhances innate antiviral immunity in mice infected with VSV, resulting in increased serum IFN‐β levels, reduced viral loads, and alleviated pulmonary inflammatory responses of the VSV‐infected mice. In conclusion, our findings highlight the potential of RBN‐2397 as a promising antiviral therapeutic agent for enhancing the IFN‐relative antiviral immune defense in host.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

TBKBP1

Basic Info

Related

Analysis