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Description

Junction-mediating and -regulatory protein (UniProt: Q8N9B5, also known as JMY) is encoded by the JMY gene (Gene ID: 133746) in human. JMY is involved in a complex pathway connecting cell motility and invasion with the p53 response to DNA damage. It is widely expressed in many types of tissue- with cytoplasmic and nuclear co-expression. It contains a unique N-terminal domain (aa 1-126) that is essential for its interaction with p300/EP300, three central coiled-coil segments (aa 324-360, 489-541, and 590-621), a polyproline region (aa 801-830), and a C-terminal WH2 domain (aa 921-938). It localizes primarily to the nucleus, but is also found at the leading edge in migrating cells. It acts both as a nuclear p53/TP53-cofactor and a cytoplasmic regulator of actin dynamics depending on conditions. In the nucleus, it acts as a cofactor that increases p53/TP53 response via its interaction with p300/EP300 and increases p53/TP53-dependent transcription and apoptosis. In the cytoplasm, it acts as a nucleation-promoting factor for both branched and unbranched actin filaments. It promotes the rapid formation of a branched actin network by first nucleating new mother filaments and then activating Arp2/3 to branch off these filaments. However, it does not affect elongation of preformed filaments. JMY is shown to be expressed in every type of tumor investigated. Overexpression of JMY in human U2OS cells is shown to induce the formation of elongated actin filament structures. JMY is ubiquitinated by MDM2 that leads to its proteasomal degradation. In case of DNA damage its interaction with MDM2 is altered that prevents its degradation and allows interaction with p300/EP300. (Ref.: Adighibe, O., et al. (2014). Virchows Arch. 465(6), 715-722, Firat-Karalar, EN., et al. (2011). Mol. Biol. Cell. 22(23), 4563-4574, Zuchero, JB., et al. (2009). Nat. Cell Biol. 11(4), 451-459).