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ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

Oncogene volume 26, pages 111–122 (2007)Cite this article

Abstract

We have recently identified ZNF185 as a gene that is downregulated in prostate cancer (PCa), in part via epigenetic alteration, and maybe associated with disease progression. In this study, we cloned the ZNF185 cDNA from normal human prostate tissues and investigated its biological function. We show that ZNF185 is a novel actin–cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain-containing protein that localizes to F-actin structures, and is enriched at focal adhesions. We find that the NH2-terminal region, which we designate the actin-targeting domain, facilitates ZNF185 binding to actin in vitro and is both necessary and sufficient to mediate actin–cytoskeleton targeting of ZNF185, whereas the LIM domain, which is localized in the COOH-terminus is dispensable for this phenomenon. Interestingly, ectopic expression of full-length ZNF185, but not a mutant lacking the actin-targeting domain, could suppress proliferation and anchorage-independent growth of PCa cells. Together, our data suggest that ZNF185 may function as a tumor-suppressor protein by associating with the actin–cytoskeleton.

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Acknowledgements

We thank Dr Daniel D Billadeau for enlightening discussions and critically reading this article, and Dr Hong Cao and Dr McNiven's laboratory for providing the FR cells. This work was supported in part by NIH Grants CA70892 and CA91956.

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  1. Department of Urology, Mayo Clinic College of Medicine, Mayo Clinic/Foundation, Rochester, MN, USA

    J-S Zhang, A Gong & C Y F Young

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  1. J-S Zhang
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Correspondence to J-S Zhang.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Zhang, JS., Gong, A. & Young, C. ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer. Oncogene 26, 111–122 (2007). https://doi.org/10.1038/sj.onc.1209769

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