Abstract
Nogo-B/ASY has been characterized as a novel human apoptosis-inducing protein without any known apoptosis-related motifs. However, the validity of Nogo-B/ASY as a physiological apoptotic protein was recently questioned. In present research, we demonstrate that ASY overexpression contributes to ER stress and induces apoptosis through ER Ca2+ depletion and ER-specific pathways. ER stress and the disorder of intracellular calcium trigger the apoptosis induced by ASY overexpression. At the same time, stable transfectants overexpressing high levels of ASY are resistant to ER-stress-associated stimuli, which implies that ASY overexpression activates protective response in response to ER stress. Our results provide a direct apoptotic pathway that ASY overexpression induces apoptosis through ER stress and ER-specific signal pathways.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptation, Physiological
-
Apoptosis / physiology*
-
Calcium / metabolism
-
Caspase 12
-
Caspases / metabolism
-
Caspases / pharmacology
-
Endoplasmic Reticulum / drug effects
-
Endoplasmic Reticulum / physiology*
-
Growth Inhibitors / metabolism
-
HeLa Cells
-
Humans
-
Intracellular Signaling Peptides and Proteins / genetics
-
Intracellular Signaling Peptides and Proteins / metabolism*
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Myelin Proteins / genetics
-
Myelin Proteins / metabolism*
-
NF-kappa B / metabolism
-
Nogo Proteins
-
Transcription Factor CHOP / metabolism
-
Transcription Factor CHOP / pharmacology
-
Transfection
-
Up-Regulation*
Substances
-
DDIT3 protein, human
-
Growth Inhibitors
-
Intracellular Signaling Peptides and Proteins
-
Membrane Proteins
-
Myelin Proteins
-
NF-kappa B
-
Nogo Proteins
-
RTN4 protein, human
-
Transcription Factor CHOP
-
CASP12 protein, human
-
Caspase 12
-
Caspases
-
Calcium