Home » Key Scientific Articles » Role of p38 and JNK MAPK signaling pathways and tumor suppressor p53 on induction of apoptosis in response to Ad-eIF5A1 in A549 lung cancer cells.

Role of p38 and JNK MAPK signaling pathways and tumor suppressor p53 on induction of apoptosis in response to Ad-eIF5A1 in A549 lung cancer cells.

Taylor CA, Zheng Q, Liu Z, Thompson JE.

Mol Cancer. 2013 May 2;12:35.

Department of Biology, University of Waterloo, 200 University Ave. W., Waterloo, ON N2L 3G1, Canada.

 

Abstract

 

BACKGROUND:

The eukaryotic translation initiation factor 5A1 (eIF5A1) is a highly conserved protein involved in many cellular processes including cell division, translation, apoptosis, and inflammation. Induction of apoptosis is the only function of eIF5A1 that is known to be independent of post-translational hypusine modification. In the present study, we investigated the involvement of mitogen- and stress-activated protein kinases duringapoptosis of A549 lung cancer cells infected with adenovirus expressing eIF5A1 or a mutant of eIF5A1 that cannot be hypusinated (eIF5A1K50A).

METHODS:

Using adenoviral-mediated transfection of human A549 lung cancer cells to over-express eIF5A1 and eIF5A1K50A, the mechanism by which unhypusinated eIF5A1 induces apoptosis was investigated by Western blotting, flow cytometry, and use of MAPK and p53 inhibitors.

RESULTS:

Phosphorylation of ERK, p38 MAPK, and JNK was observed in response to adenovirus-mediated over-expression of eIF5A1 or eIF5A1K50A, along with phosphorylation and stabilization of the p53 tumor suppressor protein. Synthetic inhibitors of p38 and JNK kinase activity, but not inhibitors of ERK1/2 or p53 activity, significantly inhibited apoptosis induced by Ad-eIF5A1. Importantly, normal lung cells were more resistant to apoptosis induced by eIF5A1 and eIF5A1K50A than A549 lung cancer cells.

CONCLUSIONS:

Collectively these data indicate that p38 and JNK MAP kinase signaling are important for eIF5A1-induced cell death and thatinduction of apoptosis was not dependent on p53 activity.

 

Go To PubMed