{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFAM122A is a highly conserved housekeeping protein that functions as an endogenous inhibitor of protein phosphatase 2A (PP2A). It directly interacts with PP2A structural and regulatory subunits (preferentially PP2A‐Aα and B55α), thereby blocking the dephosphorylation of key substrates. Moreover, FAM122A employs a conserved short helical motif that competitively inhibits substrate docking and limits access to the PP2A catalytic core, leading to enhanced polyubiquitination and degradation of the catalytic subunit. These mechanisms promote cell growth and proper cell cycle progression while also impeding appropriate DNA damage checkpoint activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of erythropoiesis, FAM122A acts as a negative regulator of erythroid differentiation. It directly binds to the C-terminal zinc finger domain of GATA1—an essential transcription factor for erythroid lineage commitment—and diminishes its chromatin occupancy on target gene promoters, thereby suppressing transcriptional activity. This inhibitory effect, along with its aberrant upregulation observed in β-thalassemia patients, highlights FAM122A’s potential as a therapeutic target for disorders associated with dyserythropoiesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in phosphatase regulation and erythroid differentiation, FAM122A is critical for maintaining genomic stability. Deletion of FAM122A leads to increased endogenous DNA damage—evidenced by elevated levels of γH2AX and enhanced formation of DNA damage foci—while also upregulating TOP2α. This regulation of TOP2α appears to sensitize cancer cells to TOP2-targeted chemotherapeutics such as etoposide and doxorubicin, suggesting that loss of FAM122A may represent a novel strategy to enhance the efficacy of these agents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Li Fan, Man-Hua Liu, Meng Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM122A, a new endogenous inhibitor of protein phosphatase 2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.11698"}], "href": "https://doi.org/10.18632/oncotarget.11698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27588481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27588481"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jason S Wasserman, Bulat Faezov, Kishan R Patel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-024-50015-7"}], "href": "https://doi.org/10.1038/s41467-024-50015-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38982062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38982062"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jing Chen, Qiong Zhou, Man-Hua Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM122A Inhibits Erythroid Differentiation through GATA1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Reports (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stemcr.2020.07.010"}], "href": "https://doi.org/10.1016/j.stemcr.2020.07.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32763160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32763160"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yin-Qi Wang, Yun-Sheng Yang, Jing Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM122A maintains DNA stability possibly through the regulation of topoisomerase IIα expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2020.112242"}], "href": "https://doi.org/10.1016/j.yexcr.2020.112242"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32866497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32866497"}]}]}]}