Natural products reveal cancer cell dependence on oxysterol-binding proteins

被引：215

作者：

Burgett, Anthony W. G. ^{[1
]}

Poulsen, Thomas B. ^{[1
]}

Wangkanont, Kittikhun ^{[1
]}

Anderson, D. Ryan ^{[1
]}

Kikuchi, Chikako ^{[1
]}

Shimada, Kousei ^{[1
]}

Okubo, Shuichi ^{[1
]}

Fortner, Kevin C. ^{[1
]}

Mimaki, Yoshihiro ^{[2
]}

Kuroda, Minpei ^{[2
]}

Murphy, Jason P. ^{[3
]}

Schwalb, David J. ^{[3
]}

Petrella, Eugene C. ^{[3
]}

Cornella-Taracido, Ivan ^{[3
]}

Schirle, Markus ^{[3
]}

Tallarico, John A. ^{[3
]}

Shair, Matthew D. ^{[1
]}

机构：

[1] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[2] Tokyo Univ Pharm & Life Sci, Sch Pharm, Tokyo, Japan

[3] Novartis Inst Biomed Res, Cambridge, MA USA

来源：

NATURE CHEMICAL BIOLOGY | 2011年 / 7卷 / 09期

关键词：

ENDOPLASMIC-RETICULUM; CHOLESTANE GLYCOSIDES; STEROL-BINDING; TUMOR-CELLS; GOLGI; TRANSPORT; 25-HYDROXYCHOLESTEROL; EXPRESSION; IDENTIFICATION; TRAFFICKING;

D O I：

10.1038/nchembio.625

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cephalostatin 1, OSW-1, ritterazine B and schweinfurthin A are natural products that potently, and in some cases selectively, inhibit the growth of cultured human cancer cell lines. The cellular targets of these small molecules have yet to be identified. We have discovered that these molecules target oxysterol binding protein (OSBP) and its closest paralog, OSBP-related protein 4L (ORP4L)-proteins not known to be involved in cancer cell survival. OSBP and the ORPs constitute an evolutionarily conserved protein superfamily, members of which have been implicated in signal transduction, lipid transport and lipid metabolism. The functions of OSBP and the ORPs, however, remain largely enigmatic. Based on our findings, we have named the aforementioned natural products ORPphilins. Here we used ORPphilins to reveal new cellular activities of OSBP. The ORPphilins are powerful probes of OSBP and ORP4L that will be useful in uncovering their cellular functions and their roles in human diseases.

引用

页码：639 / 647

页数：9

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