Valencia C Alexander, Cotten Steven W, Duan Jinzhu, Liu Rihe
School of Pharmacy and Carolina Center for Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FEBS Lett. 2008 Jan 23;582(2):286-90. doi: 10.1016/j.febslet.2007.12.019. Epub 2007 Dec 26.
Nucleobindin-1 (NUCB1) and nucleobindin-2 (NUCB2) are multifunctional proteins that interact with Ca(2+), nucleic acids and various regulatory proteins in different signaling pathways. So far, our understanding of the regulation of the biological functions of nucleobindins remains limited. In our proteome-wide selection for downstream caspase substrates, both NUCB1 and NUCB2 are found to be the downstream substrates of caspases. We report here the detailed analyses of the cleavage of nucleobindins by caspases. Significantly, the caspase cleavage sites are located exactly at one of the Ca(2+)-binding EF-hand motifs. Our results suggest that the functions of nucleobindins could be modulated by caspase-mediated cleavage in apoptosis.
核结合蛋白-1(NUCB1)和核结合蛋白-2(NUCB2)是多功能蛋白,它们在不同的信号通路中与Ca²⁺、核酸及多种调节蛋白相互作用。到目前为止,我们对核结合蛋白生物学功能调节的理解仍然有限。在我们全蛋白质组范围内对下游半胱天冬酶底物的筛选中,发现NUCB1和NUCB2都是半胱天冬酶的下游底物。我们在此报告对半胱天冬酶切割核结合蛋白的详细分析。值得注意的是,半胱天冬酶切割位点恰好位于一个Ca²⁺结合EF手基序处。我们的结果表明,在细胞凋亡过程中,核结合蛋白的功能可能通过半胱天冬酶介导的切割来调节。