TY - JOUR
T1 - Caspase-2 associates with FAN through direct interaction and overlapping functionality
AU - Forsberg, Jeremy
AU - Li, Xinge
AU - Zamaraev, Aleksey V.
AU - Panaretakis, Theocharis
AU - Zhivotovsky, Boris
AU - Olsson, Magnus
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/5/23
Y1 - 2018/5/23
N2 - Caspase-2 has been implicated in diverse cellular processes, and the identification of factors with which it interacts has steadily increased. In the present study, we report a direct interaction between caspase-2 and factor associated with neutral sphingomyelinase activation (FAN) using yeast two-hybrid screening and co-immunoprecipitation. Further, stable suppression of caspase-2 expression in HEK293T and HeLa cells enabled a systematic investigation of putative novel enzyme functionalities, especially with respect to ceramide production, cell migration, IL-6 production and vesicular homeostasis, all of which have been previously reported to be associated with FAN. Lipidomics excluded the involvement of caspase-2 in the generation of ceramide species, but caspase-2-dependent deregulation of IL-6 release, vesicular size and delayed cell relocation supported an association between caspase-2 and FAN. Collectively, these data identify a novel caspase-2-interacting factor, FAN, and expand the role for the enzyme in seemingly non-apoptotic cellular mechanisms.
AB - Caspase-2 has been implicated in diverse cellular processes, and the identification of factors with which it interacts has steadily increased. In the present study, we report a direct interaction between caspase-2 and factor associated with neutral sphingomyelinase activation (FAN) using yeast two-hybrid screening and co-immunoprecipitation. Further, stable suppression of caspase-2 expression in HEK293T and HeLa cells enabled a systematic investigation of putative novel enzyme functionalities, especially with respect to ceramide production, cell migration, IL-6 production and vesicular homeostasis, all of which have been previously reported to be associated with FAN. Lipidomics excluded the involvement of caspase-2 in the generation of ceramide species, but caspase-2-dependent deregulation of IL-6 release, vesicular size and delayed cell relocation supported an association between caspase-2 and FAN. Collectively, these data identify a novel caspase-2-interacting factor, FAN, and expand the role for the enzyme in seemingly non-apoptotic cellular mechanisms.
KW - Caspase-2
KW - Cell migration
KW - Ceramide specie
KW - FAN
KW - Lysozyme
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U2 - 10.1016/j.bbrc.2018.03.230
DO - 10.1016/j.bbrc.2018.03.230
M3 - Article
C2 - 29621545
AN - SCOPUS:85045745372
SN - 0006-291X
VL - 499
SP - 822
EP - 828
JO - Biochemical and biophysical research communications
JF - Biochemical and biophysical research communications
IS - 4
ER -