Identification of ROCK1 kinase as a critical regulator of Beclin1 mediated autophagy during metabolic stress

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Identification of ROCK1 kinase as a critical regulator of Beclin1 mediated autophagy during metabolic stress

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Title: Identification of ROCK1 kinase as a critical regulator of Beclin1 mediated autophagy during metabolic stress
Author: Gurkar, Aditi U.; Chu, Kiki; Raj, Lakshmi; Bouley, Richard; Lee, Seung-Hwan; Kim, Young-Bum; Dunn, Sandra E.; Mandinova, Anna; Lee, Sam W.

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Citation: Gurkar, Aditi U., Kiki Chu, Lakshmi Raj, Richard Bouley, Seung-Hwan Lee, Young-Bum Kim, Sandra E. Dunn, Anna Mandinova, and Sam W. Lee. 2013. “Identification of ROCK1 kinase as a critical regulator of Beclin1 mediated autophagy during metabolic stress.” Nature communications 4 (1): 2189. doi:10.1038/ncomms3189. http://dx.doi.org/10.1038/ncomms3189.
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Abstract: The Ser/Thr Rho kinase 1 (ROCK1) is known to play major roles in a wide range of cellular activities, including those involved in tumor metastasis and apoptosis. Here we identify an indispensable function of ROCK1 in metabolic stress-induced autophagy. Applying a proteomics approach, we characterize Beclin1, a proximal component of the PI(3)kinase class III lipid-kinase complex that induces autophagy, as an interacting partner of ROCK1. Upon nutrient deprivation, activated ROCK1 promotes autophagy by binding and phosphorylating Beclin1 at Thr119. This results in the specific dissociation of the Beclin1-Bcl-2 complex, without affecting the Beclin1-UVRAG interaction. Conversely, inhibition of ROCK1 activity increases Beclin1-Bcl-2 association, thus reducing nutritional stress-mediated autophagy. Genetic knockout of ROCK1 function in mice also leads to impaired autophagy as evidenced by reduced autophagosome formation. These results show that ROCK1 acts as a prominent upstream regulator of Beclin1-mediated autophagy and maintains a homeostatic balance between apoptosis and autophagy.
Published Version: doi:10.1038/ncomms3189
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740589/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879651
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