Abstract
Mammalian STE20-like kinase 1 (MST1) (so-named for its similarity to the yeast mitogen-activated protein kinase kinase kinase kinase STE20) is activated during apoptosis. In fact, it appears to be a direct target of caspases. Cleavage of the enzyme by caspases, along with phosphorylation, contributes to activation of the enzyme. Ura et al. now show that proteolytic removal of the COOH-terminus of the enzyme not only relieves inhibition of the enzyme, but also removes two nuclear export signals and thus causes localization of MST1 to the nucleus. Studies of mutants directed into or out of the nucleus showed that accumulation of MST1 in the nucleus is associated with increased chromatin condensation. Expression of a dominant-negative catalytically inactive mutant of MST1 inhibited chromatin condensation in 293T cells treated with staurosporin (an apoptotic stimulus). Also, a mutant of MST1 that cannot be cleaved was less effective in causing chromatin condensation when overexpressed in cultured cells. The results reveal a new mechanism for regulating nuclear localization of an enzyme and support a role for MST1 in mediating nuclear signals that lead to apoptosis. S. Ura, N. Masuyama, J. D. Graves, Y. Gotoh, Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. Proc. Natl. Acad. Sci. U.S.A. 98 , 10148-10153 (2001) [Abstract] [Full Text]
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