{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPSMC3IP, also known as TBPIP or Hop2, is a nuclear protein that plays a key role in meiotic homologous recombination. Working as part of the Hop2–Mnd1 complex, it stimulates the strand exchange activity of the recombinases Rad51 and Dmc1, thereby ensuring proper homology matching and alignment of chromosomes during meiosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nIn addition to its recombination function, PSMC3IP serves as a tissue‐specific coactivator for several nuclear receptors. It interacts with the DNA‐binding domains of receptors such as estrogen, androgen, glucocorticoid, progesterone, and thyroid hormone receptors to enhance ligand‐driven transcription. Disruption of its C-terminal domain, which is critical for this coactivation, can abolish estrogen-mediated transcription and is implicated in ovarian dysgenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n\nPSMC3IP is also important for reproductive development and fertility. Genetic studies have linked mutations in this gene not only to XX female gonadal dysgenesis but also to defects that may underlie conditions such as azoospermia and premature ovarian insufficiency. In these contexts, loss or impairment of PSMC3IP function disrupts hormone-driven folliculogenesis and normal gonadal development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n\nBeyond its roles in meiosis and steroid hormone receptor regulation, PSMC3IP has been implicated in oncogenesis. Studies in ovarian and hepatocellular carcinomas indicate that aberrant expression of PSMC3IP may promote tumor cell proliferation, facilitate cell survival by modulating DNA repair pathways, and affect the response to genotoxic stress, including radiosensitivity. In head and neck squamous cell carcinoma, for example, altered PSMC3IP expression is linked to changes in homologous recombination repair gene networks and cancer stem cell characteristics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rima Enomoto, Takashi Kinebuchi, Makoto Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506506200"}], "href": "https://doi.org/10.1074/jbc.M506506200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16407260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16407260"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tetsurou Satoh, Takahiro Ishizuka, Takuya Tomaru, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tat-binding protein-1 (TBP-1), an ATPase of 19S regulatory particles of the 26S proteasome, enhances androgen receptor function in cooperation with TBP-1-interacting protein/Hop2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2008-1122"}], "href": "https://doi.org/10.1210/en.2008-1122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19325002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19325002"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David Zangen, Yotam Kaufman, Sharon Zeligson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes coactivation of estrogen-driven transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.09.006"}], "href": "https://doi.org/10.1016/j.ajhg.2011.09.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21963259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21963259"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Toshinobu Miyamoto, Eitetsu Koh, Naoko Sakugawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two single nucleotide polymorphisms in PRDM9 (MEISETZ) gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-008-9270-x"}], "href": "https://doi.org/10.1007/s10815-008-9270-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18941885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18941885"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "A Norling, A L Hirschberg, L Karlsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "No mutations in the PSMC3IP gene identified in a Swedish cohort of women with primary ovarian insufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sex Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000357605"}], "href": "https://doi.org/10.1159/000357605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24481226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24481226"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Libin Mei, Lingling Huang, Yanru Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two novel biallelic mutations in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PSMC3IP"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " in a patient affected by premature ovarian insufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2021.12561"}], "href": "https://doi.org/10.3892/mmr.2021.12561"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34878148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34878148"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Min Peng, Hao Zhang, Lahcen Jaafar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human ovarian cancer stroma contains luteinized theca cells harboring tumor suppressor gene GT198 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.485581"}], "href": "https://doi.org/10.1074/jbc.M113.485581"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24097974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24097974"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jingli Ding, Yang Li, Huxiong Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of PSMC3IP suppresses the proliferation and xenografted tumorigenesis of hepatocellular carcinoma cell."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.27824"}], "href": "https://doi.org/10.1002/jcb.27824"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30362169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30362169"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jacqueline Nathansen, Vasyl Lukiyanchuk, Linda Hein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-021-01842-1"}], "href": "https://doi.org/10.1038/s41388-021-01842-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34079088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34079088"}]}]}]}