Natural products reveal cancer cell dependence on oxysterol-binding proteins.
Natural products reveal cancer cell dependence on oxysterol-binding proteins.
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DOI：
10.1038/nchembio.625
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发表时间：
2011-08-07
影响因子：
14.8
通讯作者：
Shair, Matthew D.
中科院分区：
文献类型：
--
作者：
Burgett, Anthony W. G.;Poulsen, Thomas B.;Wangkanont, Kittikhun;Anderson, D. Ryan;Kikuchi, Chikako;Shimada, Kousei;Okubo, Shuichi;Fortner, Kevin C.;Mimaki, Yoshihiro;Kuroda, Minpei;Murphy, Jason P.;Schwalb, David J.;Petrella, Eugene C.;Cornella-Taracido, Ivan;Schirle, Markus;Tallarico, John A.;Shair, Matthew D.
头孢他汀1、OSW-1、ritterazine B和schweinfurthin A是天然产物，其有效地并且在某些情况下选择性地抑制培养的人癌细胞系的生长。这些小分子的细胞靶点尚未确定。我们已经发现这些分子靶向氧固醇结合蛋白（OSBP）及其最接近的partial，OSBP相关蛋白4L（ORP 4L）-蛋白质不知道参与癌细胞存活。OSBP和ORF构成了一个进化上保守的蛋白质超家族，其成员参与信号传导、脂质转运和脂质代谢。然而，OSBP和ORP的功能在很大程度上仍然是个谜。根据我们的研究结果，我们将上述天然产物命名为ORPphilins。在这里，我们使用ORPphilins来揭示OSBP的新细胞活性。亲ORPins是OSBP和ORP 4L的强有力探针，将有助于揭示它们的细胞功能及其在人类疾病中的作用。
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.
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