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Zfra translocates to the mitochondria and blocks cytochrome c release during the opening of mitochondrial membrane permeability transition pores
Author(s) -
Chang NanShan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a507-a
Subject(s) - mitochondrial permeability transition pore , mitochondrion , chemistry , cytochrome c , biophysics , microbiology and biotechnology , inner mitochondrial membrane , permeability (electromagnetism) , membrane , biology , biochemistry , apoptosis , programmed cell death
A key event in apoptosis is cytochrome c release from the mitochondria. Here it is demonstrated that Zfra, a 31‐amino‐acid C2H2 zinc finger‐like protein, runs against this rule and yet induces apoptosis when overexpressed. Apoptotic stress induces phosphorylation of Zfra at serine 8, which is essential for apoptosis. Upon inducing the opening of mitochondrial membrane permeability pores with staurosporine, atractyloside and betulinic acid, Zfra becomes Ser8‐phosphorylated and tranalocates to the mitochondria, along with proapoptotic p53 and WOX1. Compared to control cells, Zfra blocks cytochrome c release. Zfra induces the expression of proteins in the cell cycle progression toward G2/M such as cyclin B and ?‐tubulin, downregulates Bcl‐2 and Bcl‐x (without activating caspases), and sustains phosphorylation of ERK and JNK1. The sustained activation of ERK and JNK1 may induce cell death. Thus, Zfra initiates a novel cell death pathway independently of apaf/cytochrome c/caspases.