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

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

  • Biochim Biophys Acta Mol Cell Res. 2018 Jul 30;S0167-4889(18)30188-5. doi: 10.1016/j.bbamcr.2018.07.013.
Rituparna Chaudhuri 1,  Kritika Khanna 1,  D Koundinya 1,  Bijay Pattnaik 2,  Damini Vatsa 3,  Anurag Agrawal 1,  Balaram Ghosh 4
Affiliations

Affiliations

  • 1 Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007,India.; Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
  • 2 Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007,India.; Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
  • 3 Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007,India.
  • 4 Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007,India.; Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.. Electronic address: bghosh14@gmail.com.
PMID: 30071275 DOI: 10.1016/j.bbamcr.2018.07.013
Abstract

Inositol polyphosphate 4 Phosphatase type I Enzyme (INPP4A) has a well-documented function in the cytoplasm where it terminates the phosphatidylinositol 3-kinase (PI 3-K) pathway by acting as a negative regulator. 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.

Keywords

Apoptosis; INPP4A; Nuclear localization; Nucleocytoplasmic shuttling; Proliferation.

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