NRC -interacting factor 1 interacts with p35 and regulates neuronal differentiation

Cdk5, a proline-directed serine/threonine kinase, plays a critical role during neuronal development. The activity of Cdk5 depends on its association with two regulatory partners, p35 or p39, which are prominently expressed in neural tissues. Recent emerging studies suggest an involvement of Cdk5 in nuclear functions. Several proteins that are involved in transcriptional regulation including p53, myocyte enhancer factor-2, signal transducer and activator of transcription-3 as well as mSds3 have been demonstrated to be the substrates for Cdk5. We have recently identified another nuclear protein, NRC-interacting factor 1 (NIF-1) as one of the interacting proteins of p35. NIF-1 is suggested to regulate the transcriptional activity through its interaction with nuclear hormone receptor coregulator (NRC). Interestingly, we found that p35 regulates the shuttling of NIF-1 between nucleus and cytoplasm. Furthermore, we found that the nuclear export of NIF-1 mediated by p35 is CRM1-dependent. NIF-1 protein is prominently expressed in neurons at early embryonic stages and declined during development. To explore the functions of NIF-1, we silenced the NIF-1 protein in neurons using siRNA approach and found that NIF-1 is required for the neuronal differentiation and neurite outgrowth, Taken together, the identification of NIF-1 as p35-interacting protein further supports an important role of Cdk5 in nuclear function and provides insights into understanding how Cdk5 regulates neuronal differentiation.