title: Stabilization of the survival motor neuron protein by ASK1.
abstract: The survival motor neuron (SMN) is a spliceosomal snRNP-interacting protein that was initially identified as a defective molecule in spinal muscular atrophy (SMA). The disease severity of SMA is determined by SMN protein level. Here, we show that apoptosis signal-regulating kinase 1 (ASK1) stabilizes SMN protein by inhibiting SMN poly-ubiquitination, and that the kinase activity of ASK1 is less important than its ability to bind to SMN. Furthermore, depletion of ASK1 by RNA interference revealed that ASK1 modulates neurite outgrowth by regulating SMN protein level in NSC34 motor neuron-like cells. Collectively, our results suggest that ASK1 acts as a novel binding partner of SMN and controls the steady-state level of SMN through complex formation with SMN in neurite outgrowth.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Kwon
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D016501:Neurites / Q000378:metabolism; D025821:Polyubiquitin / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D034622:RNA Interference; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; D025821:Polyubiquitin; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human