| First Author | Lin YM | Year | 2008 |
| Journal | J Cell Sci | Volume | 121 |
| Issue | Pt 14 | Pages | 2382-93 |
| PubMed ID | 18577580 | Mgi Jnum | J:139740 |
| Mgi Id | MGI:3810003 | Doi | 10.1242/jcs.021394 |
| Citation | Lin YM, et al. (2008) eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions. J Cell Sci 121(Pt 14):2382-93 |
| abstractText | 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. |
