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Author Notes:

Changliang Shan, Phone: +86-2085222787, Email: changliangshan@jnu.edu.cn

S.Z. and K.Y. contributed to conception and design; S.Z., C.B.C., and K.Y. contributed to development of methodology; S.Z., H.S., X.Z., Q.Q., C.S., and K.Y. contributed to analysis and interpretation of data; S.Z., C.S., and K.Y. contributed to writing, review, and/or revision of the manuscript; K.Y. contributed to study supervision.

The authors declare that they have no conflict of interest.


Research Funding:

The work is supported by a grant from NIH (RO1 DK09092) to C.B.C., NIH (RO1 CA186918) to K.Y., National Natural Science Foundation of China (No. 81672781) and the Fundamental Research Funds for the Central Universities (21616323) to S.Z., National Natural Science Foundation of China (No. 81702746) to L.L., The Fundamental Research Funds for the Central Universities (21617433), the Science and Technology Program of Guangdong (Grant 2017A030313890) and the Science and Technology Program of Guangzhou (Grant 201807010003) to C.S.

This work was also supported by the Program of Introducing Talents of Discipline to Universities (111 Project, No. B16021).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • 14-3-3 PROTEINS
  • AKT

Cellular energy stress induces AMPK-mediated regulation of glioblastoma cell proliferation by PIKE-A phosphorylation

Journal Title:

Cell Death and Disease


Volume 10, Number 3


, Pages 222-222

Type of Work:

Article | Final Publisher PDF


Phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A), which associates with and potentiates Akt activity, is a pro-oncogenic factor that play vital role in cancer cell survival and growth. However, PIKE-A physiological functions under energy/nutrient deficiency are poorly understood. The AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that is a principal regulator of energy homeostasis and has a critical role in metabolic disorders and cancers. In this present study, we show that cellular energy stress induces PIKE-A phosphorylation mediated by AMPK activation, thereby preventing its carcinogenic action. Moreover, AMPK directly phosphorylates PIKE-A Ser-351 and Ser-377, which become accessible for the interaction with 14-3-3β, and in turn stimulates nuclear translocation of PIKE-A. Nuclear PIKE-A associates with CDK4 and then disrupts CDK4-cyclinD1 complex and inhibits the Rb pathway, resulting in cancer cell cycle arrest. Our data uncover a molecular mechanism and functional significance of PIKE-A phosphorylation response to cellular energy status mediated by AMPK.

Copyright information:

© 2019, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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