Transforming growth factor β-activated protein kinase 1 (TAK1)-binding protein 2 (TAB2) and its close homolog TAB3 are initially characterized as adapter proteins essential for TAK1 activation in response to interleukin-1β and tumour necrosis factor-α. However, the physiological roles of TAB2 and TAB3 are still not fully understood. Here we report that TAB2 and TAB3 bind to Beclin1 and colocalize in the cytoplasm. TAB2 also interacts with ATG13 and is phosphorylated by ULK1. Overexpression of TAB2 or TAB3 induces punctate localization of ATG5 under the normal culture condition. Knockdown of TAB2 and TAB3 results in the decrease in endogenous protein level of p62/SQSTM1 under the normal culture condition, while overexpression of TAB2 results in the accumulation of p62/SQSTM1 independently of TAK1. The decrease of p62/SQSTM1 induced by the knockdown of TAB2 and TAB3 is largely dependent on ATG5. These results suggest that TAB2 and TAB3 negatively regulate autophagy independently of TAK1 activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jb/mvr123 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis.
J Cell Biol
January 2025
State Key Laboratory of Virology, RNA Institute, College of Life Sciences and Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) exhibit differences in their inflammatory responses and pulmonary damage, yet the specific mechanisms remain unclear. Here, we discovered that the SARS-CoV-2 nucleocapsid (N) protein inhibits the activation of the nuclear factor-κB (NF-κB) pathway and downstream signal transduction by impeding the assembly of the transforming growth factor β-activated kinase1 (TAK1)-TAK1 binding protein 2/3 (TAB2/3) complex. In contrast, the SARS-CoV N protein does not impact the NF-κB pathway.
View Article and Find Full Text PDFRegulation of TAK-TAB Complex Activation through Ubiquitylation.
Front Biosci (Landmark Ed)
April 2024
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 250100 Jinan, Shandong, China.
Transforming growth factor-β (TGF-β) activated kinase 1 (TAK1), also named mitogen-activated protein kinase 7 (MAPK7), forms a pivotal signaling complex with TAK1-binding proteins (TAB1, TAB2, and TAB3), orchestrating critical biological processes, including immune responses, cell growth, apoptosis, and stress responses. Activation of TAK1 by stimuli, such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and Toll-like receptors (TLRs), underscores its central role in cellular signaling. Given the critical role of the TAK1-binding protein (TAK1-TAB) complex in cellular signaling and its impact on various biological processes, this review seeks to understand how ubiquitination thoroughly regulates the TAK1-TAB complex.
View Article and Find Full Text PDFTAK1-binding protein 2 (TAB2) and TAB3 are redundantly required for TLR-induced cytokine production in macrophages.
Int Immunol
August 2024
Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0213, Japan.
Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in innate and adaptive immunity. TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways downstream of diverse immune receptors, including toll-like receptors (TLRs). Upon stimulation with TLR ligands, TAK1 is activated via recruitment to the lysine 63-linked polyubiquitin chain through TAK1-binding protein 2 (TAB2) and TAB3.
View Article and Find Full Text PDFMolecular mechanisms of HCG18 in the sorafenib resistance of hepatocellular carcinoma.
Anticancer Drugs
January 2024
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Gannan Medical University.
Sorafenib has been approved for advance hepatocellular carcinoma (HCC), however, drug resistance often occurred. Therefore, it is of great significance to clarify the underlying mechanisms of sorafenib resistance and to find out the effective strategies to overcome sorafenib resistance. The expression of HCG18 was detected by qPCR, MTT, colony formation, flow cytometry and TUNEL assay were used to explore the function of HCG18 on sorafenib resistance in HCC.
View Article and Find Full Text PDFFluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats.
Nat Commun
February 2023
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, 130012, Changchun, China.
In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!