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Int. J. Mol. Sci. 2018, 19(2), 466; https://doi.org/10.3390/ijms19020466

BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells

1
Department of Neurosurgery, International University of Health and Welfare School of Medicine, Atami 413-0012, Japan
2
Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
3
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
4
Keio Advanced Research Centers, Keio University, Tsukuba 300-2611, Japan
*
Author to whom correspondence should be addressed.
Received: 22 December 2017 / Revised: 29 January 2018 / Accepted: 2 February 2018 / Published: 5 February 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: BC-box motif; BC-box protein; skin-derived precursors; neuronal differentiation BC-box motif; BC-box protein; skin-derived precursors; neuronal differentiation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kanno, H.; Xu, Y.; Miyakawa, T.; Kubo, A.; Higashida, T.; Kobayashi, N.B.; Yoshida, T.; Tanokura, M. BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells. Int. J. Mol. Sci. 2018, 19, 466.

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