A functional genome-wide RNAi screen identifies TAF1 as a regulator for apoptosis in response to genotoxic stress

41Citations
Citations of this article
52Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Evasion from apoptotic cell death is a characteristic of cancer; genes that modulate this process may be optimal for therapeutic attack. Identifying key regulators of apoptosis is thus a central goal in cancer therapy. Here, we describe a loss-of-function screen that uses RNA interference libraries to identify genes required for induction of apoptosis. We used a short-hairpin RNA expressing vector with high gene-expression silencing activity that contained fetal brain cDNAs. Survived cells from genotoxic stress were isolated to determine knock-down of molecules that are crucial for induction of apoptosis. We identified TBP-associated factor 1 (TAF1), a gene previously implicated as an essential component of transcription machinery. Depletion of TAF1 was associated with substantial attenuation of apoptosis induced by oxidative as well as genotoxic stress. Microarray analysis further demonstrated that a number of genes were transcriptionally declined in cells silenced for TAF1. Surprisingly, knocking down TAF1 exhibited a marked decrease in p27Kip1 expression, allowing cells resistant from oxidative stress-induced apoptosis. These results suggest that TAF1 regulates apoptosis by controlling p27Kip1 expression. Our system provides a novel approach to identifying candidate genes that modulate apoptosis.

Cite

CITATION STYLE

APA

Kimura, J., Nguyen, S. T., Liu, H., Taira, N., Miki, Y., & Yoshida, K. (2008). A functional genome-wide RNAi screen identifies TAF1 as a regulator for apoptosis in response to genotoxic stress. Nucleic Acids Research, 36(16), 5250–5259. https://doi.org/10.1093/nar/gkn506

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free