BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells.
Von Hippel-Lindau tumor suppressor protein (pVHL) functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs) and skin-derived precursors (SKPs). Here we identified a neuronal differentiation domain (NDD) in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the ... NDD. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by Janus kinase-2 (JAK2) ubiquitination of JAK2 and inhibition of the JAK2/the signal transducer and activator of transcription-3(STAT)3 pathway. The NDD in pVHL contained the BC-box motif ((A,P,S,T)LXXX (A,C) XXX(A,I,L,V)) corresponding to the binding site of elongin C. Therefore, we proposed that other BC-box proteins might also contain an NDD; and subsequently also identified in them an NDD containing the amino-acid sequence encoded by the BC-box motif in BC-box proteins. Furthermore, we showed that different NDD peptide-delivered cells differentiated into different kinds of neuron-like cells. That is, dopaminergic neuron-like cells, cholinergic neuron-like cells, GABAnergic neuron-like cells or rhodopsin-positive neuron-like cells were induced by different NDD peptides. These novel findings might contribute to the development of a new method for promoting neuronal differentiation and shed further light on the mechanism of neuronal differentiation of somatic stem cells.
Mesh Terms:
Amino Acid Motifs, Animals, Animals, Newborn, Cell Differentiation, Cholinergic Neurons, Dermis, Dopaminergic Neurons, Elongin, GABAergic Neurons, Gene Expression Regulation, Injections, Intraventricular, Intercellular Signaling Peptides and Proteins, Janus Kinase 2, Peptides, Protein Binding, Protein Domains, Rats, Rats, Wistar, STAT3 Transcription Factor, Signal Transduction, Stem Cells, Von Hippel-Lindau Tumor Suppressor Protein
Amino Acid Motifs, Animals, Animals, Newborn, Cell Differentiation, Cholinergic Neurons, Dermis, Dopaminergic Neurons, Elongin, GABAergic Neurons, Gene Expression Regulation, Injections, Intraventricular, Intercellular Signaling Peptides and Proteins, Janus Kinase 2, Peptides, Protein Binding, Protein Domains, Rats, Rats, Wistar, STAT3 Transcription Factor, Signal Transduction, Stem Cells, Von Hippel-Lindau Tumor Suppressor Protein
Int J Mol Sci
Date: Feb. 05, 2018
PubMed ID: 29401731
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