Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10412 (H1.4)
 75 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysine methylation is one of the most prominent histone posttranslational modifications that regulate chromatin structure. Changes in histone lysine methylation status have been observed during cancer formation, which is thought to be a consequence of the dysregulation of histone lysine methyltransferases or the opposing demethylases. KDM4/JMJD2 proteins are demethylases that target histone H3 on lysines 9 and 36 and histone H1.4 on lysine 26. This protein family consists of three ~130-kDa proteins (KDM4A-C) and KDM4D/JMJD2D, which is half the size, lacks the double PHD and Tudor domains that are epigenome readers and present in the other KDM4 proteins, and has a different substrate specificity. Various studies have shown that KDM4A/JMJD2A, KDM4B/JMJD2B, and/or KDM4C/JMJD2C are overexpressed in breast, colorectal, lung, prostate, and other tumors and are required for efficient cancer cell growth. In part, this may be due to their ability to modulate transcription factors such as the androgen and estrogen receptor. Thus, KDM4 proteins present themselves as novel potential drug targets. Accordingly, multiple attempts are under way to develop KDM4 inhibitors, which could complement the existing arsenal of epigenetic drugs that are currently limited to DNA methyltransferases and histone deacetylases.
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PMID:KDM4/JMJD2 histone demethylases: epigenetic regulators in cancer cells. 2364 28

KDM4A, KDM4B and KDM4D are lysine demethylases which demethylate H3 at lysine K9 and K36 sites, additionally KDM4D also the H1.4 linker histone at K26 lysine. Lysine methylation changes can repress or induce gene expression at specific sites thus influencing cellular functions. We analysed the immunohistochemical expression of KDM4A, KDM4B and KDM4D in a clinical material of 188 patients with lung carcinomas. There were 132 (70%) squamous cell carcinomas, 53 (28%) adenocarcinomas and 3 (2%) large cell carcinomas in the study. Additionally, the trimethylated state of chromatin was detected with an antibody to trimethylated H3K9 residue. Nuclear KDM4A and KDM4D were associated with the presence of lymph node metastases in tumors. Cytoplasmic KDM4A was associated with poor survival of the patients (P = 0.015) and with a shorter recurrence free interval (P = 0.028). KDM4A and KDM4D appear to have a significant role in the metastatic spread of lung carcinomas. The findings are also in line with their proposed involvement in mechanisms associated with cell proliferation, apoptosis and DNA repair.
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PMID:KDM4A, KDM4B and KDM4C in non-small cell lung cancer. 2672 85