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J Biol Chem. 2013 Apr 26;288(17):11887-96. doi: 10.1074/jbc.M112.425702. Epub 2013 Mar 13.

Dual functions for cytosolic α-mannosidase (Man2C1): its down-regulation causes mitochondria-dependent apoptosis independently of its α-mannosidase activity.

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  • 1Glycometabolome Team, Systems Glycobiology Research Group, RIKEN Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.


Cytosolic α-mannosidase (Man2C1) trims free oligosaccharides in mammalian cells, and its down-regulation reportedly delays cancer growth by inducing mitotic arrest or apoptosis. However, the mechanism by which Man2C1 down-regulation induces apoptosis is unknown. Here, we demonstrated that silencing of Man2C1 via small hairpin RNAs induced mitochondria-dependent apoptosis in HeLa cells. Expression of CHOP (C/EBP homologous protein), a transcription factor critical to endoplasmic reticulum stress-induced apoptosis, was significantly up-regulated in Man2C1 knockdown cells. However, this enhanced CHOP expression was not caused by endoplasmic reticulum stress. Interestingly, Man2C1 catalytic activity was not required for this regulation of apoptosis; introduction of mutant, enzymatically inactive Man2C1 rescued apoptotic phenotypes of Man2C1 knockdown cells. These results show that Man2C1 has dual functions: one in glycan catabolism and another in apoptotic signaling.

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