Abstract
Abstract ENC1 (ectodermal neuronal cortex 1) is a BTB/Kelch domain-containing protein, whose gene was originally identified in a p53-overexpressing cell line, and was later found to show abnormal expression in various tumor tissues. Here, we report that ENC1 is a new regulator that links DNA-damage signals to apoptosis. ENC1 is induced in different cancer cells by DNA-damage signals. The induced ENC1 protein then interacted with cullin-3 and retinoblastoma protein (Rb), forming an E3 ubiquitin ligase complex and ubiquitinating Rb protein. Upon ubiquitination, Rb protein failed to interact with E2F, allowing for transcriptional activation of E2F-dependent genes. Inhibition of ENC1 by RNA interference or by a dominant-negative mutant attenuated Rb ubiquitination, E2F-depedent gene activation, as well as apoptosis induced by DNA-damage signals. However, epitopic overexpression of ENC1 gene activated E2F-dependent genes, but failed to trigger apoptosis. Deletion and mutation analysis shows that a conserved motif located within Kelch domain at the C-terminus is essential for regulation of Rb function and apoptosis in response to DNA-damage signals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 264. doi:1538-7445.AM2012-264
Published Version
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