7jm5

<table><tr><td colspan='2'>[[7jm5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JM5 FirstGlance]. <br>

== Function ==

[https://www.uniprot.org/uniprot/KDM4B_HUMAN KDM4B_HUMAN] Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate.<ref>PMID:16603238</ref>

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== Publication Abstract from PubMed ==

Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3-Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B (KDM4B) is a therapeutic vulnerability for PAX3-FOXO1(+) RMS. Genetic and pharmacologic inhibition of KDM4B substantially delayed tumor growth. Suppression of KDM4 proteins inhibited the expression of core oncogenic transcription factors and caused epigenetic alterations of PAX3-FOXO1-governed superenhancers. Combining KDM4 inhibition with cytotoxic chemotherapy led to tumor regression in preclinical PAX3-FOXO1(+) RMS subcutaneous xenograft models. In summary, we identified a targetable mechanism required for maintenance of the PAX3-FOXO1-related transcription factor network, which may translate to a therapeutic approach for fusion-positive RMS.

Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma.,Singh S, Abu-Zaid A, Jin H, Fang J, Wu Q, Wang T, Feng H, Quarni W, Shao Y, Maxham L, Abdolvahabi A, Yun MK, Vaithiyalingam S, Tan H, Bowling J, Honnell V, Young B, Guo Y, Bajpai R, Pruett-Miller SM, Grosveld GC, Hatley M, Xu B, Fan Y, Wu G, Chen EY, Chen T, Lewis PW, Rankovic Z, Li Y, Murphy AJ, Easton J, Peng J, Chen X, Wang R, White SW, Davidoff AM, Yang J Sci Transl Med. 2022 Jul 13;14(653):eabq2096. doi: 10.1126/scitranslmed.abq2096. , Epub 2022 Jul 13. PMID:35857643<ref>PMID:35857643</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Homo sapiens]]