Noxa와 Mcl-1의 상호작용이 Noxa에 의한 세포사의 조절

Abstract

The Bcl-2 family proteins play critical roles in regulation of apoptosis, and the interaction of pro- and anti-apoptotic member is important to determine the fate of cells. Noxa belong to a Bcl-2 homology 3 (BH3)-only member of pro-apoptotic Bcl-2 family member. It has been originally identified to be upregulated by p53 in response to DNA damage. To understand the mechanism by which Noxa-induced cell death is regulated, we screened the binding partner using the yeast two hybrid screening. We found that Mcl-1 binds to Noxa. The binding of Noxa to Mcl-1 was confirmed by immunoprecipitation with anti-Mcl-1 in HCT 116 cells. Since Mcl-1 is known to inhibit cell death through interaction with anti-apoptotic Bcl-2 family members, we investigated whether Mcl-1 can inhibit the Noxa-induced cell death. As expected, Mcl-1 significantly inhibits the Noxa-induced cell death in HCT 116 cells. To find out the mechanism, we investigated degradation of Mcl-1 by Noxa. Mcl-1 degradation was inhibited by z-VAD-fmk, a pan-caspase inhibitor. The results suggest that Mcl-1 might be a necessary event in Noxa-induced cell death.