By inhalation might result in an increased release of preformed mediators as Crizotinib indicated by elevated triggering capacity. Amyloid precursor protein binding protein-1 has been known to interact with the intracellular carboxyl terminus of the amyloid precursor protein, the precursor protein of amyloid beta peptide, which is the main component of neuritic plaques in Alzheimer’s disease,,. APP-BP1, like APP, is ubiquitously expressed in neural and non-neural tissues. The intracellular C-terminal domain of APP interacts with several proteins, including the Fe65 protein family, JNK interacting protein 1, X11, APP-BP1, and others. Although extensive research has been done to characterize the normal physiological function of APP and its interaction with the proteins described above, there are many aspects that still require clarification. APP-BP1 is localized to human chromosome 16 band q22 and acts as one component of the bipartite activating enzyme for the ubiquitin-like small molecule, NEDD 8,,. Upon binding to Uba3, which is homologous to the carboxyl terminus of E1, APP-BP1 acts as an activating enzyme, thus activating NEDD8. APP-BP1/Uba3 also interacts with the N-terminus of the conjugating enzyme Ubc12, which is analogous to E2 in the uniquitination pathway,,,. Neddylation is involved in various cellular functions including cell cycle progression,,. Several targets for neddylation exists in mammalian cells, including the cullin family members, a major constituent of the ubiquitin-ligase, Skp-1Cul-1-F box complex,. SCF ubiquitin ligase targets p27, the cyclin-dependent kinase inhibitor, for degradation during the transition of cells from the G0/G1 phase to the S phase of the cell cycle, and also regulate PDCD4, Cdc25A, Claspin, Wee1, Emi1, cyclin E, and cyclin D1, all of which are key substrates within the cell division cycle,. Overexpression of APP-BP1 in primary neurons induces apoptosis and increases DNA synthesis. In addition, upregulated APP-BP1 expression has been observed in the lipid rafts in the hippocampi of AD brains, when compared with agematched control brains. In this study, we focused on the role for APP-BP1 in neural stem cell cycle progression, and demonstrated that APP-BP1 is critically required for cell cycle progression. This action of APPBP1 is antagonistically regulated by the interaction with APP. Additionally, phosphorylation of APP at the threonine 668 residue was found to be required for the interaction with APPBP1. Since APP-BP1 was first identified as a protein that interacts with APP, numerous studies have investigated its functions as well as its possible pathological roles in AD. APP-BP1 has been reported to be one component of bipartite enzyme complex, together with hUba3 and to be involved in SCF complex activation.