14-3-3Tau regulates Beclin 1 and is required for autophagy.
BACKGROUND
Beclin 1 plays an essential role in autophagy; however, the regulation of Beclin 1 expression remains largely unexplored. An earlier ChIP-on-chip study suggested Beclin 1 could be an E2F target. Previously, we also reported that 14-3-3tau regulates E2F1 stability, and is required for the expression of several E2F1 target genes. 14-3-3 proteins mediate many cellular signaling processes, but its role in autophagy has not been investigated. We hypothesize that 14-3-3tau could regulate Beclin 1 expression through E2F1 and thus regulate autophagy.


RESULTS
Using the RNAi technique we demonstrate a novel role for one of 14-3-3 isoforms, 14-3-3tau, in the regulation of Beclin 1 expression and autophagy. Depletion of 14-3-3tau inhibits the expression of Beclin 1 in many different cell lines; whereas, upregulation of 14-3-3tau induces Beclin 1. The regulation is physiologically relevant as an extracellular matrix protein tenascin-C, a known 14-3-3tau inducer, can induce Beclin 1 through 14-3-3tau. Moreover, rapamycin-induced, serum free-induced and amino acid starvation-induced autophagy depends on 14-3-3tau. We also show the expression of Beclin 1 depends on E2F, and E2F can transactivate the Beclin 1 promoter in a promoter reporter assay. Upregulation of Beclin 1 by 14-3-3tau requires E2F1. Depletion of E2F1, like 14-3-3tau, also inhibits autophagy.


CONCLUSIONS
Taken together, this study uncovers a role for 14-3-3tau in Beclin 1 and autophagy regulation probably through regulation of E2F1.
Wang
Bing
B
Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Ling
Shiyun
S
Lin
Weei-Chin
WC
D048948:14-3-3 Proteins / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001343:Autophagy; D000071186:Beclin-1; D002460:Cell Line; D045744:Cell Line, Tumor; D050687:E2F1 Transcription Factor / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D020033:Protein Isoforms; D015533:Transcriptional Activation
D048948:14-3-3 Proteins; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms
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