The NRIF3 Family of Transcriptional Coregulators Induces Rapid and Profound Apoptosis in Breast Cancer Cells

生資一 鮑岳洋 39328009

Abstract

Nuclear receptor–interacting factor 3(NRIF3) was originally found as a coactivator in HeLa cell for thyroid hormone receptor(TR) and retinoid X receptor(RXR). Surprisingly, we find that the NRIF3 also can induce rapidly and profound apoptosis in the breast cancer cell. A novel death domain (DD1) which was mapped to a short 30-aminoacid region common to all members of the NRIF3 family may play an important a role in this apoptosis mechanism. According to the experimental consequences, NRIF3-induced apoptosis occurs through a novel caspase 2-mediated pathway that involves mitochondrial membrane permeabilization(MMP) but does not require other caspases. The cytotoxicity of NRIF3 and DD1 appears to be cell type specific, as they selectively kill breast cancer or related cells but not other examined cells of different origins. Strategies utilizing NRIF3 and/or DD1 and/or targeting this death switch may lead to the development of novel and more selective therapeutics against breast cancer.

Author: Dangsheng Li, Sharmistha Das, Tatsuya Yamada, and Herbert H. Samuels

Source: http://mcb.asm.org/cgi/content/full/24/9/3838?view=full&pmid=15082778

MOLECULAR AND CELLULAR BIOLOGY, May 2004, p. 3838–3848

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