期刊
PLOS ONE
卷 5, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0010409
关键词
-
资金
- National Institutes of Health [CA 100857, CA138641]
- Department of Defense [W81XWH-09-1-0338]
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 14-3-3 tau 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 14-3-3 tau could regulate Beclin 1 expression through E2F1 and thus regulate autophagy. Methods and Findings: Using the RNAi technique we demonstrate a novel role for one of 14-3-3 isoforms, 14-3-3 tau, in the regulation of Beclin 1 expression and autophagy. Depletion of 14-3-3 tau inhibits the expression of Beclin 1 in many different cell lines; whereas, upregulation of 14-3-3 tau induces Beclin 1. The regulation is physiologically relevant as an extracellular matrix protein tenascin-C, a known 14-3-3 tau inducer, can induce Beclin 1 through 14-3-3 tau. Moreover, rapamycin-induced, serum free-induced and amino acid starvation-induced autophagy depends on 14-3-3 tau. 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 14-3-3 tau requires E2F1. Depletion of E2F1, like 14-3-3 tau, also inhibits autophagy. Conclusion: Taken together, this study uncovers a role for 14-3-3 tau in Beclin 1 and autophagy regulation probably through regulation of E2F1.
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