Nucling mediates apoptosis by inhibiting expression of galectin-3 through interference with nuclear factor kappaB signalling.

Abstract

Nucling is a novel apoptosis-associated molecule, which is involved with cytochrome c /Apaf-1/caspase-9 apoptosome induction following pro-apoptotic stress. In the present study, we show first that Nucling is able to interact with galectin-3. Galectin-3 is known to participate in many biological processes, including apoptotic cell death. Nucling was found to down-regulate the expression level of galectin-3 mRNA/protein. Nucling-deficient cells, in which galectin-3 expression is up-regulated, appeared to be resistant to some forms of pro-apoptotic stress as compared with wild-type cells. In addition, the preputial gland from Nucling-deficient mice expressed a significant level of galectin-3 and exhibited a high incidence of inflammatory lesions, indicating that Nucling plays a crucial role in the homoeostasis of this gland by interacting with the galectin-3 molecule and regulating the expression level of galectin-3. Up-regulation of galectin-3 was also observed in the heart, kidney, lung, testis and ovary of the Nucling-deficient mice. In order to confirm the functional interaction between Nucling and galectin-3, a well-documented candidate for the mediator of galectin-3 expression, NF-kappaB (nuclear factor kappaB), was investigated as well. Nucling was shown to interfere with NF-kappaB activation via the nuclear translocation process of NF-kappaB/p65, thus inhibiting the expression of galectin-3. Taken together, we propose that Nucling mediates apoptosis by interacting and inhibiting expression of galectin-3.