Compartmentalized cellular functions of KDM4A.

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KDM4A levels affect the distribution of translation initiation factors

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Compartmentalized cellular functions of KDM4A. Compartmentalized cellular functions of KDM4A. Cartoon depicting the known nuclear and newly uncovered cytoplasmic roles of KDM4A. Shown are receptor tyrosine kinase (RTK) and glucose signaling axes that elicit control on mTORC1, a key regulator of protein synthesis. Van Rechem and colleagues show that KDM4A regulates protein synthesis in the cytoplasm through its association with translation initiation factors. They further show that an identified SNP-482 in KDM4A promotes its turnover by targeting it to the SCF ubiquitin ligase complex. Loss of KDM4A or inhibition of catalytic activity with a small molecule (JIB-04) enhances therapeutic effects of rapamycin and other mTORC1 inhibitors. Scott B. Rothbart et al. Cancer Discovery 2015;5:228-230 ©2015 by American Association for Cancer Research