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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Lin YM,Chen YR,Lin JR,Wang WJ,Inoko A,Inagaki M,Wu YC,Chen RH

doi

10.1242/jcs.021394

subject

Has Abstract

pub_date

2008-07-15 00:00:00

pages

2382-93

issue

Pt 14

eissn

0021-9533

issn

1477-9137

pii

jcs.021394

journal_volume

121

pub_type

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