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http://dx.doi.org/10.5352/JLS.2007.17.8.1063

Mcl-1 is a Binding Partner of hNoxa  

Park, Sun-Young (Department of Biochemistry and Medical Science and Engineering Research Center for Resistant Cells, Chosun University School of Medicine)
Kim, Tae-Hyoung (Department of Biochemistry and Medical Science and Engineering Research Center for Resistant Cells, Chosun University School of Medicine)
Publication Information
Journal of Life Science / v.17, no.8, 2007 , pp. 1063-1067 More about this Journal
Abstract
The Bcl-2 family proteins play critical roles in regulation of apoptosis, and the balanced interaction of pro- and anti-death members is a key factor in determining the cell fate. Noxa, a BH3-only Bcl-2-family member, has been originally identified as a target gene of p53. To understand the mechanism by which human Noxa (hNoxa) regulates the cell death, we screened the hNoxa binding partner using the yeast two hybrid screening and found that anti-death protein Mcl-1 binds to hNoxa. The binding of hNoxa to Mcl-1 was confirmed by immunoprecipitation in human colon cancer cell line HCT 116 cells. Mcl-1 significantly inhibited the hNoxa-induced cell death in HCT 116 cells. During the cell death induced by hNoxa, Mcl-1 protein was degraded. Its degradation was inhibited by z-VAD-fmk, a pancaspase inhibitor, suggesting caspase is responsible for Mcl-1 degradation in response to hNoxa. Together, the results indicate that hNoxa binds to Mcl-1 that is degraded by cas-pases during hNoxa-induced cell death.
Keywords
hNoxa; Mcl-1; Bcl-2 family; p53; apoptosis;
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