{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPASD1 is a cancer/testis antigen with multiple roles in cellular regulation and oncogenesis. It was initially identified as a repressor of circadian rhythms, acting through its evolutionary relationship with CLOCK by directly interacting with the CLOCK:BMAL1 transcriptional complex to suppress its activity—a function normally restricted to germline tissues that becomes pathologically activated upon oncogenic transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, PASD1 functions as a positive regulator of transcription by enhancing STAT3 activation. In the nucleus, PASD1 competes with the phosphatase TC45 for binding to STAT3, thereby inhibiting STAT3 dephosphorylation and potentiating pro-oncogenic gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in transcriptional regulation, PASD1 has been exploited as a promising immunotherapeutic target in cancer. PASD1-based DNA fusion vaccines, which link immunogenic domains such as the fragment C of tetanus toxin to PASD1 sequences, have been shown to trigger potent cytotoxic T-lymphocyte responses in multiple myeloma models, resulting in the effective lysis of tumor cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, specific PASD1 peptides have demonstrated immunogenicity in colorectal cancer, enabling the activation of CD8+ T cells that can recognize and kill PASD1-expressing tumor cells, further establishing PASD1 as a viable target for cancer immunotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, PASD1 expression is markedly elevated in glioma, where its overexpression correlates with higher tumor grade, increased p53 expression, and poorer prognosis. Functional studies indicate that downregulation of PASD1 in glioma cells causes cell cycle arrest at the G2/M phase and induces apoptosis by modulating key regulators of cell proliferation and death, thereby confirming its oncogenic role in glioma tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alicia K Michael, Stacy L Harvey, Patrick J Sammons, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cancer/Testis Antigen PASD1 Silences the Circadian Clock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2015.03.031"}], "href": "https://doi.org/10.1016/j.molcel.2015.03.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25936801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25936801"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhi-Sheng Xu, Hong-Xia Zhang, Yu-Long Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jmcb/mjw005"}], "href": "https://doi.org/10.1093/jmcb/mjw005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26892021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26892021"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "D Joseph-Pietras, Y Gao, N Zojer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA vaccines to target the cancer testis antigen PASD1 in human multiple myeloma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2010.196"}], "href": "https://doi.org/10.1038/leu.2010.196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20861911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20861911"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Joanne Ec Soh, Nadiah Abu, Ismail Sagap, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunotherapy (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2217/imt-2019-0073"}], "href": "https://doi.org/10.2217/imt-2019-0073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31478431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31478431"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ruoyan Li, Mengguo Guo, Laijun Song "}, {"type": "b", "children": [{"type": "t", "text": "PAS Domain Containing Repressor 1 (PASD1) Promotes Glioma Cell Proliferation Through Inhibiting Apoptosis In Vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/MSM.916308"}], "href": "https://doi.org/10.12659/MSM.916308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31558691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31558691"}]}]}]}