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Originally published as MBC in Press, 10.1091/mbc.E06-09-0869 on May 30, 2007

Vol. 18, Issue 8, 3015-3025, August 2007

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Evidence that Mono-ADP-Ribosylation of CtBP1/BARS Regulates Lipid StorageFormula Formula

René Bartz*, Joachim Seemann*, John K. Zehmer*, Ginette Serrero{dagger}, Kent D. Chapman{ddagger}, Richard G.W. Anderson*, and Pingsheng Liu*

*Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039; {dagger}A&G Pharmaceutical Inc., Columbia, MD 21045; and {ddagger}Department of Biological Sciences, University of North Texas, Denton, TX 76203

Submitted September 27, 2006; Revised May 7, 2007; Accepted May 17, 2007
Monitoring Editor: Vivek Malhotra

Mono-ADP-ribosylation is emerging as an important posttranslational modification that modulates a variety of cell signaling pathways. Here, we present evidence that mono-ADP-ribosylation of the transcriptional corepressor C terminal binding protein, brefeldin A (BFA)-induced ADP-ribosylated substrate (CtBP1/BARS) regulates neutral lipid storage in droplets that are surrounded by a monolayer of phospholipid and associated proteins. CtBP1/BARS is an NAD-binding protein that becomes ribosylated when cells are exposed to BFA. Both endogenous lipid droplets and droplets enlarged by oleate treatment are lost after 12-h exposure to BFA. Lipid loss requires new protein synthesis, and it is blocked by multiple ribosylation inhibitors, but it is not stimulated by disruption of the Golgi apparatus or the endoplasmic reticulum unfolded protein response. Small interfering RNA knockdown of CtBP1/BARS mimics the effect of BFA, and mouse embryonic fibroblasts derived from embryos that are deficient in CtBP1/BARS seem to be defective in lipid accumulation. We conclude that mono-ADP-ribosylation of CtBP1/BARS inactivates its repressor function, which leads to the activation of genes that regulate neutral lipid storage.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-09-0869) on May 30, 2007.

Formula Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Richard G.W. Anderson (richard.anderson{at}utsouthwestern.edu).







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