Aminoacylase 1 is a sphingosine kinase 1-interacting protein.
Sphingosine kinase type 1 (SphK1) and its product sphingosine-1-phosphate have been shown to promote cell growth and inhibit apoptosis of tumor cells. In an effort to further understand the regulation of SphK1, we used a yeast two-hybrid screen to find SphK1-interacting proteins. One of these was identified as aminoacylase 1 (Acy1), a metalloenzyme that removes amide-linked acyl groups from amino acids and may play a role in regulating responses to oxidative stress. Both the C-terminal fragment found in the two-hybrid screen and full-length Acy1 co-immunoprecipitate with SphK1. Though both C-terminal and full-length proteins slightly reduce SphK1 activity measured in vitro, the C-terminal fragment inhibits while full-length Acy1 potentiates the effects of SphK1 on proliferation and apoptosis. Interestingly, Acy1 induces redistribution of SphK1 as observed by immunocytochemistry and subcellular fractionation. Collectively, our data suggest that Acy1 physically interacts with SphK1 and may influence its physiological functions.
Maceyka
Michael
M
Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Nava
Victor E
VE
Milstien
Sheldon
S
Spiegel
Sarah
S
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques; D000099157:Sphingosine Kinase
D000581:Amidohydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase; C019672:aminoacylase I