{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWASHC2A (also known as FAM21) is a critical regulator of endosomal sorting, functioning as part of the WASH complex to ensure proper cargo recycling. It directly interacts with SNX27 and retromer, thereby establishing and maintaining a specialized endosomal subdomain that prevents cargo misrouting to lysosomes and the Golgi apparatus. This role in coordinating endosome-to–plasma membrane recycling is essential for sustaining cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "In addition to its cytoplasmic functions, nuclear processes implicate WASHC2A in tumorigenesis. Studies have shown that ligand-activated IGF1R translocates to the nucleus and binds to chromatin, where it associates with transcription start sites of genes, including the WASHC2A gene. Upregulation of WASHC2A contributes to tumor cell survival and migration, highlighting a novel mechanism by which IGF signaling influences cancer biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "Beyond its roles in vesicular trafficking and transcriptional regulation, WASHC2A is instrumental in the DNA damage response. It interacts via its C-terminal region with the Ku protein, a key component in non-homologous end joining (NHEJ). This interaction is crucial for recruiting the WASH complex to sites of DNA double strand breaks, thereby facilitating efficient repair and contributing to the preservation of genomic integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Seongju Lee, Jaerak Chang, Craig Blackstone "}, {"type": "b", "children": [{"type": "t", "text": "FAM21 directs SNX27-retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10939"}], "href": "https://doi.org/10.1038/ncomms10939"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26956659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26956659"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tamara Aleksic, Nicki Gray, Xiaoning Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear IGF1R Interacts with Regulatory Regions of Chromatin to Promote RNA Polymerase II Recruitment and Gene Expression Associated with Advanced Tumor Stage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-17-3498"}], "href": "https://doi.org/10.1158/0008-5472.CAN-17-3498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29735545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29735545"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tao Wang, Ai-Xue Zheng, Ping Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM21 interacts with Ku to promote the localization of WASH to DNA double strand break sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Repair (Amst) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dnarep.2023.103603"}], "href": "https://doi.org/10.1016/j.dnarep.2023.103603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38029687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38029687"}]}]}]}