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Photo-Activatable Akt Probe: A New Tool to Study the Akt-Dependent Physiopathology of Cancer Cells

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Title: Photo-Activatable Akt Probe: A New Tool to Study the Akt-Dependent Physiopathology of Cancer Cells
Authors: Haga, Sanae Browse this author →KAKEN DB
Ozawa, Takeaki Browse this author
Morita, Naoki Browse this author
Asano, Mami Browse this author
Jin, Shigeki Browse this author
Yimin Browse this author →KAKEN DB
Ozaki, Michitaka Browse this author →KAKEN DB
Keywords: Photo-activatable probe
Akt
Nutritional deprivation
Oxidative stress
Issue Date: 10-Apr-2018
Publisher: Cognizant Communication Corporation
Journal Title: Oncology research
Volume: 26
Issue: 3
Start Page: 467
End Page: 472
Publisher DOI: 10.3727/096504017X15040166233313
PMID: 28933316
Abstract: Akt is commonly overexpressed and activated in cancer cells and plays a pivotal role in cell survival, protection, and chemoresistance. Therefore, Akt is one of the target molecules in understanding characters of cancer cells and developing anticancer drugs. Here we examined whether a newly developed photo-activatable Akt (PA-Akt) probe, based on a light-inducible protein interaction module of plant cryptochrome2 (CRY2) and cryptochrome-interacting basic helix-loop-helix (CIB1), can regulate Akt-associated cell functions. By illuminating blue light to the cells stably transfected with PA-Akt probe, CRY2-Akt (a fusion protein of CRY2 and Akt) underwent a structural change and interacted with Myr-CIBN (myristoylated N-terminal portion of CIB1), anchoring it at the cell membrane. Western blot analysis revealed that 5473 and T308 of the Akt of probe-Akt were sequentially phosphorylated by intermittent and continuous light illumination. Endogenous Akt and GSK-3 beta, one of the main downstream signals of Akt, were also phosphorylated, depending on light intensity. These facts indicate that photo-activation of probe-Akt can activate endogenous Akt and its downstream signals. The photo-activated Akt conferred protection against nutritional deprivation and H2O2 stresses to the cells significantly. Using the newly developed PA-Akt probe. endogenous Akt was activated easily, transiently, and repeatedly. This probe will be a unique tool in studying Akt-associated specific cellular functions in cancer cells and developing anticancer drugs.
Rights: http://creativecommons.org/licenses/by-nc/3.0/
Type: article
URI: http://hdl.handle.net/2115/70690
Appears in Collections:保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 尾崎 倫孝

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