eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions.

Abstract

Keratins 8 and 18 (collectively referred to as K8/K18) are the major components of intermediate filaments of simple epithelial cells. Recent studies have revealed the function of K8/K18 in apoptosis modulation. Here, we show that eIF3k, originally identified as the smallest subunit of eukaryotic translation initiation factor 3 (eIF3) complexes, also localizes to keratin intermediate filaments and physically associates with K18 in epithelial cells. Upon induction of apoptosis, eIF3k colocalizes with K8/K18 in the insoluble cytoplasmic inclusions. Depletion of endogenous eIF3k de-sensitizes simple epithelial cells to various types of apoptosis through a K8/K18-dependent mechanism and promotes the retention of active caspase 3 in cytoplasmic inclusions by increasing its binding to keratins. Consequently, the cleavage of caspase cytosolic and nuclear substrates, such as ICAD and PARP, respectively, is reduced in eIF3k-depleted cells. This study not only reveals the existence of eIF3k in a subcellular compartment other than the eIF3 complex, but also identifies an apoptosis-promoting function of eIF3k in simple epithelial cells by relieving the caspase-sequestration effect of K8/K18, thereby increasing the availability of caspases to their non-keratin-residing substrates.

DOI: 10.1242/jcs.021394

Cite this paper

@article{Lin2008eIF3kRA, title={eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions.}, author={Yu-Min Lin and Yi-Ru Chen and Jia-Ren Lin and Won-Jing Wang and Akihito Inoko and Masaki Inagaki and Yi-Chun Wu and R . - H . Chen}, journal={Journal of cell science}, year={2008}, volume={121 Pt 14}, pages={2382-93} }