The Study of Signaling Pathways Controlling Neuronal Apoptosis Inhibitory Protein (NAIP) Expression and Function

摘要

Deletions in the gene for neuronal apoptosis inhibitory protein (NAIP) have been suggested to exacerbate the severity of motor neuron loss in patients with spinal muscular atrophy. NAIP is the founding mammalian member of the inhibitor of apoptosis (IAP) protein family that is characterized by highly conserved amino-terminai motifs called baculovirus IAP repeats (BIRs). Previous in vitro and in vivo analyses with an adenovirus expressing NAIP but lacking exons 14 and 17 of the full-length cDNA (NAIPAE14/17) displayed measurable cytoprotection against apoptotic-induced cell death. In the present study, cytoprotective effects were obtained with adeno-NAIPAE14/17 alone in the human neuroblastoma SH-SYSY. Pretreatment of these cells with trophic factors failed to improve the cytoprotection mediated by NAIP. Similarly, the anti-apoptotic effect of NAIP was observed in HeLa cells transiently transfected with constructs expressing fuil-lengthNAIP and NAIPAE14/17. To further investigate NAIP's