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

Correspondence: Dr J-S Zhang, Department of Urology, Mayo Clinic College of Medicine, Mayo Clinic/Foundation, 200 First St. SW, Rochester, MN 55905, USA. E-mail: zhang.jinsan@mayo.edu

Received 18 February 2006; Revised 24 April 2006; Accepted 24 April 2006; Published online 26 June 2006.

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.