Novel nuclear translocation of inositol polyphosphate 4-phosphatase is associated with cell cycle, proliferation and survival

In this study, we demonstrate for the first time that INPP4A shuttles between the cytoplasm and the nucleus. Nuclear INPP4A is enzymatically active and in dynamic equilibrium between the nucleus and cytoplasm depending on the cell cycle stage, with highest amounts detected in the nucleus during the G0/G1 phase. Moreover, nuclear INPP4A is found to have direct proliferation suppressive activity. Cells constitutively overexpressing nuclear INPP4A exhibit massive apoptosis. In human tissues as well as cell lines, lower nuclear localization of INPP4A correlate with cancerous growth. Together, our findings suggest that nuclear compartmentalization of INPP4A may be a mechanism to regulate cell cycle progression, proliferation and apoptosis. Our results imply a role for nuclear-localized INPP4A in tumor suppression in humans.Graphical abstractSchematic model depicting the possible role of nuclear INPP4A in regulating cell proliferation and apoptosis. In this proposed model, INPP4A shuttles between the cytosol and the nucleus under normal conditions and ratio between the two compartments is maintained depending upon the cell's requirement. Transient nuclear localization of INPP4A is essential to the maintenance of normal proliferation. In cancerous condition, INPP4A fails to localize to the nucleus. This may occur due to a dysregulated import-export machinery. This, in turn, contributes to loss of cell cycle control, aberrant growth and onset of oncogenic event.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research