期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 228, 期 1, 页码 182-189出版社
WILEY
DOI: 10.1002/jcp.24120
关键词
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资金
- NIH/NIDDK [R01 DK052131, R01 DK052131-14S1]
- National Institutes of Health [R01 DK052131, R01 DK052131-14S1]
Human antigen R (HuR) is a post-transcriptional regulator of gene expression that plays a key role in stabilizing mRNAs during cellular stress, leading to enhanced survival. HuR expression is tightly regulated through multiple transcription and post-transcriptional controls. Although HuR is known to stabilize a subset of mRNAs involved in cell survival, its role in the survival pathway of PI3-kinase/Akt signaling is unclear. Here, we show that in renal proximal tubule cells, HuR performs a central role in cell survival by amplifying Akt signaling in a positive feedback loop. Key to this feedback loop is HuR-mediated stabilization of mRNA encoding Grb10, an adaptor protein whose expression is critical for Akt activation. Stimulation of Akt by interaction with Grb10 then activates NF-?B, which further enhances HuR mRNA and protein expression. This feedback loop is active in unstressed cells, but its effects are increased during stress. Therefore, this study demonstrates a central role for HuR in Akt signaling and reveals a mechanism by which modest changes in HuR levels below or above normal may be amplified, potentially resulting in cell death or cellular transformation. J. Cell. Physiol. 228: 182189, 2013. (c) 2012 Wiley Periodicals, Inc.
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