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Target intelligence / Profile preview
Tankyrase 1 binding protein 1 (TNKS1BP1)
- Target
- TNKS1BP1
- Molecular classification
- Other (protein-protein interaction scaffold), Tankyrase binding partner
01
Overview
Tankyrase 1 binding protein 1 (TNKS1BP1) is a protein that binds to the ankyrin domain of tankyrase 1, modulating protein ubiquitination, DNA repair, autophagy, and lipid metabolism. It is implicated in cancer progression and resistance to immunotherapy. TNKS1BP1 interacts with various partners such as TRIM21 (ubiquitin ligase) and CNOT4, driving K48- or K6-linked polyubiquitination and subsequent protein degradation. TNKS1BP1 is upregulated in advanced tumors and correlates with poor outcome in hepatocellular carcinoma, making it both a prognostic biomarker and a candidate therapeutic target. Experimental knockdown in cancer models synergizes with anti-PD-L1 immunotherapies, enhances antitumor immunity, and restricts tumor growth, mainly by altering the tumor immune microenvironment via the JAK2/STAT3/PD-L1 pathway.
- Other names
- TAB182KIAA1741182 kDa tankyrase-1-binding proteinFLJ45975CNOT12testis secretory sperm-binding protein Li 206a
02
Mechanism of action
Inhibition or knockdown of TNKS1BP1 can synergize with PD-L1 blockade, improve immune cell infiltration, and augment cytotoxic T cell activity against tumors by modulating the JAK2/STAT3/PD-L1 pathway
03
Biological functions
DNA damage response and double-strand break repairProtein ubiquitination and degradation via interaction with TRIM21 and CNOT4Regulation of autophagy and lipid metabolismMediator of cell proliferation, invasion, metastasis, and radioresistance in cancer
04
Disease associations
Cancer (hepatocellular carcinoma, esophageal squamous cell carcinoma, breast cancer, lung cancer)Therapy resistance (radioresistance, immune evasion, resistance to anti-PD-L1 immunotherapies)Alcohol-induced mental disorderCherubism
05
Safety considerations
Therapeutic targeting may affect DNA repair capacity and normal cell cycle progression, raising potential off-target effects related to genome integrity and immune modulation
06
Interacting drugs
Anti-PD-L1 antibodies (e.g., mouse PD-L1 antibody A2115 used in knockout and synergy experiments)
07
Biomarkers
TNKS1BP1 expression as a predictor of poor prognosis and therapy resistance in hepatocellular carcinoma
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