Ask about this productRelated genes to: TMEM173 Blocking Peptide
- Gene:
- TMEM173 NIH gene
- Name:
- transmembrane protein 173
- Previous symbol:
- -
- Synonyms:
- FLJ38577, NET23, ERIS, MPYS, STING, MITA
- Chromosome:
- 5q31.2
- Locus Type:
- gene with protein product
- Date approved:
- 2006-08-24
- Date modifiied:
- 2019-04-23
Related products to: TMEM173 Blocking Peptide
Related articles to: TMEM173 Blocking Peptide
- The activation of stimulator of interferon genes (STING) for the treatment of cancer is a long-standing therapeutic goal. However, the clinical use of orthosteric STING agonists has shown limited utility in patients with advanced/metastatic cancer. C92 is a potent representative of a first-in-class chemical series of allosteric small-molecule human STING agonists that are distinguished by their binding site which lies within STING's proton channel and their consequently unique functional properties. This study characterizes the pharmacology and the anticancer efficacy of C92. - Source: PubMed
Publication date: 2026/06/23
Banerjee MonaliMiddya Sandip KumarShrivastava RiteshMiddya AninditaPryde David CChakraborty DebjaniSoram ThanilsanaMane NagaswamyRawat NidhiGautam AnujPuniya KavitaSharma PritiYadav Dharmendra BSônego FabianeThiam KaderMills James EMani ShyamalaGhosh RajibBasu SouravSurya Arjun - Ferroptosis has emerged as a key effector mechanism in antitumor immunity, yet the transcellular metabolic cross talk that modulates ferroptotic sensitivity in colorectal cancer (CRC) remains incompletely understood. Here, we describe an integrative regulatory axis linking immune cell-intrinsic Stimulator of Interferon Genes (STING) signaling to tumor ferroptosis through coordinated lipid metabolism and posttranslational modifications (PTMs). Mechanistically, STING activation in immune cells triggers TANK-binding kinase 1 (TBK1)-dependent phosphorylation of cytosolic phospholipase A (cPLA) at Ser505, thereby releasing arachidonic acid (AA) into the tumor microenvironment (TME). This immune-derived AA is taken up by adjacent CRC cells, where it promotes ACSL4-dependent ferroptosis by inhibiting EP300-mediated lactylation of ACSL4 at lysine 426 (K426). In vivo, pharmacological activation of STING enhances AA release and facilitates ferroptosis-mediated tumor suppression. Notably, STING agonist synergizes with PD-1 checkpoint blockade to inhibit tumor progression, which is reversed by the ferroptosis inhibitor. Collectively, our findings establish an integrative and transcellular immunometabolic framework linking innate immune sensing to tumor ferroptosis, providing a strong rationale for combinatorial therapeutic strategies in CRC. - Source: PubMed
Publication date: 2026/06/23
Ding LinaDu WenqiZhu JingZhang YuxiangWang XingyueLi LinfengLiu BuhuiWang XiaohongWang QinglingPei Dongsheng - The E3 ubiquitin ligase APC/C with its coactivator Cdh1 is generally considered to be a tumor suppressor, regulating genome stability and the G/S transition of the cell cycle. Cdh1 enhances the stability of immune-cell checkpoint ligand PD-L1 to modulate adaptive immunity. Here, we explored its role in innate immune regulation and identified a noncanonical, degradation-independent function of Cdh1 in clear cell renal cell carcinoma (ccRCC) through its stabilization of the cytosolic double-stranded DNA (dsDNA) sensor STING. Protein levels of Cdh1 and STING were concurrently increased in ccRCC samples from patients, and Cdh1 depletion reduced the abundance and half-life of STING protein in ccRCC cell lines. Mechanistically, Cdh1 bound to the destruction-box degron motif of STING, which sterically prevented the binding of the E3 ubiquitin ligase SPOP, thereby protecting STING from degradation. Upon stimulation of STING with an agonist or dsDNA, Cdh1 bound to STING at the Golgi and increased its abundance and signaling activity. Pharmacologically inhibiting kinases that phosphorylate Cdh1 increased STING abundance and STING-mediated type 1 interferon signaling in ccRCC cells, presumably by promoting the formation of APC/C-Cdh1-STING complexes. These findings reveal a Cdh1-STING axis in ccRCC that might be therapeutically exploited to potentiate antitumor innate immunity. - Source: PubMed
Publication date: 2026/06/23
Zhu ZhichuanHahn QuentinTurbiville Lila ELiu Pengda - Lysine lactylation (Kla) is a lactate-derived post-translational modification that has emerged as a critical metabolic-epigenetic regulator linking cellular metabolic states to innate immune signaling. The cGAS-STING pathway, a central cytosolic DNA-sensing mechanism essential for antiviral defense, antitumor immunity, and inflammatory regulation, is profoundly influenced by the metabolic milieu. However, the precise role of lactylation in modulating this pathway remains to be systematically synthesized. - Source: PubMed
Publication date: 2026/06/20
Wang HongquanWang ZhijiMeng FanyuGao YingZhang MingZhang WeiWang ErdanShi KeruiJin Yuzi - The endoplasmic reticulum (ER) is a hub for several essential functions, including lipid metabolism, macroautophagy/autophagy, and innate immune signaling. Excess ER generated during a stress response is degraded by a selective type of autophagy known as ERphagy/reticulophagy. A recent study provides a mechanism by which cholesterol levels regulate ERphagy, STING1 activation, and cholesterol biosynthesis. Elevated ER cholesterol levels suppress ERphagy by reducing RETREG1/FAM134B interactions with the autophagy-related protein MAP1LC3/LC3 and the lysosomal protein LAMP2. The study shows that cholesterol directly binds to RETREG1 and SCAP, facilitating the formation of the RETREG1-SCAP complex. Sequestration of RETREG1 in this manner prevents it from performing its ERphagy functions. Furthermore, RETREG1 also interacts with STING1 and is important for its activation in response to viral infections. SCAP-RETREG1 complex formation also reduces the STING1 response. Thus, this study links lipid metabolism, innate immunity, and autophagy, emphasizing a central role for cholesterol in these processes. - Source: PubMed
Publication date: 2026/06/19
Govind Chhabi KKlionsky Daniel J