Stabilization of the Survival Motor Neuron Protein by ASK1

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.