Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis

Adam B. Castoreno; Yegor Smurnyy; Angelica D. Torres; Martha S. Vokes; Thouis R. Jones; Anne E. Carpenter; Ulrike Eggert

doi:10.1038/nchembio.363

Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis

Adam B. Castoreno, Yegor Smurnyy, Angelica D. Torres, Martha S. Vokes, Thouis R. Jones, Anne E. Carpenter, Ulrike Eggert

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

Abstract

We report the discovery of small molecules that target the Rho pathway, which is a central regulator of cytokinesis-the final step in cell division. We have developed a way of targeting a small molecule screen toward a specific pathway, which should be widely applicable to the investigation of any signaling pathway. In a chemical genetic variant of a classical modifier screen, we used RNA interference (RNAi) to sensitize cells and identified small molecules that suppressed or enhanced the RNAi phenotype. We discovered promising candidate molecules, which we named Rhodblock 1-8, and we identified the target of Rhodblock 6 as Rho kinase. Several Rhodblocks inhibited one function of the Rho pathway in cells: the correct localization of phosphorylated myosin light chain during cytokinesis. Rhodblocks differentially perturb Rho pathway proteins in cells and can be used to dissect the mechanism of the Rho pathway during cytokinesis.

Original language	English
Pages (from-to)	457-463
Number of pages	7
Journal	Nature Chemical Biology
Volume	6
Issue number	6
Early online date	2 May 2010
DOIs	https://doi.org/10.1038/nchembio.363
Publication status	Published - Jun 2010

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title = "Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis",

abstract = "We report the discovery of small molecules that target the Rho pathway, which is a central regulator of cytokinesis-the final step in cell division. We have developed a way of targeting a small molecule screen toward a specific pathway, which should be widely applicable to the investigation of any signaling pathway. In a chemical genetic variant of a classical modifier screen, we used RNA interference (RNAi) to sensitize cells and identified small molecules that suppressed or enhanced the RNAi phenotype. We discovered promising candidate molecules, which we named Rhodblock 1-8, and we identified the target of Rhodblock 6 as Rho kinase. Several Rhodblocks inhibited one function of the Rho pathway in cells: the correct localization of phosphorylated myosin light chain during cytokinesis. Rhodblocks differentially perturb Rho pathway proteins in cells and can be used to dissect the mechanism of the Rho pathway during cytokinesis.",

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AU - Castoreno, Adam B.

AU - Smurnyy, Yegor

AU - Torres, Angelica D.

AU - Vokes, Martha S.

AU - Jones, Thouis R.

AU - Carpenter, Anne E.

AU - Eggert, Ulrike

PY - 2010/6

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AB - We report the discovery of small molecules that target the Rho pathway, which is a central regulator of cytokinesis-the final step in cell division. We have developed a way of targeting a small molecule screen toward a specific pathway, which should be widely applicable to the investigation of any signaling pathway. In a chemical genetic variant of a classical modifier screen, we used RNA interference (RNAi) to sensitize cells and identified small molecules that suppressed or enhanced the RNAi phenotype. We discovered promising candidate molecules, which we named Rhodblock 1-8, and we identified the target of Rhodblock 6 as Rho kinase. Several Rhodblocks inhibited one function of the Rho pathway in cells: the correct localization of phosphorylated myosin light chain during cytokinesis. Rhodblocks differentially perturb Rho pathway proteins in cells and can be used to dissect the mechanism of the Rho pathway during cytokinesis.

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