{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProper regulation of transmembrane proteins is essential for maintaining tissue homeostasis, as evidenced in diverse contexts such as neurodegeneration and immune cell development. In amyotrophic lateral sclerosis, astrocytes contribute to motor neuron vulnerability by downregulating major histocompatibility complex class I molecules, while in the thymus, natural killer (NK) receptor homologues are implicated in the modulation of immune signaling. These studies highlight the broader importance of cell surface receptor regulation in both neural and immune environments."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA novel player in receptor regulation is ENTREP1, formerly known as FAM189A2, which has been identified as an activator of the HECT-type ubiquitin ligase ITCH. ENTREP1 is a transmembrane protein harboring PPxY motifs that mediate its association with ITCH, thereby enhancing ITCH-mediated ubiquitination of substrates such as the chemokine receptor CXCR4. This modification facilitates CXCR4 endocytosis, thus desensitizing receptor signaling and modulating downstream chemotactic responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in receptor turnover, ENTREP1 appears to exert tumor suppressive functions in lung adenocarcinoma. Studies have shown that ENTREP1 expression is diminished in lung cancer tissues, and restoration of its levels leads to upregulation of key tight junction proteins (OCLN and TJP2) alongside a reduction in CXCR4 expression. These alterations are associated with inhibited cellular activity and shifts in the tumor immune microenvironment, suggesting that ENTREP1 contributes to maintaining cellular integrity and modulating anti-tumor immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "SungWon Song, Carlos J Miranda, Lyndsey Braun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.4052"}], "href": "https://doi.org/10.1038/nm.4052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26928464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26928464"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alice Y Welch, Masanori Kasahara, Lisa M Spain "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the mouse killer immunoglobulin-like receptor-like (Kirl) gene family mapping to chromosome X."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunogenetics (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00251-002-0529-6"}], "href": "https://doi.org/10.1007/s00251-002-0529-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12618911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12618911"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Takumi Tsunoda, Miho Riku, Norika Yamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ENTREP/FAM189A2 encodes a new ITCH ubiquitin ligase activator that is downregulated in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.202051182"}], "href": "https://doi.org/10.15252/embr.202051182"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34927784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34927784"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jiakun Liu, Wei Zhao, Yanchao Luan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM189A2 plays a tumour suppressor role in lung adenocarcinoma by influencing cell apoptosis, CXCR4 expression and tight junction proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Cell (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tice.2024.102441"}], "href": "https://doi.org/10.1016/j.tice.2024.102441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38878656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38878656"}]}]}]}