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Open AccessArticle

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.
Int. J. Mol. Sci. 2018, 19(2), 466; https://doi.org/10.3390/ijms19020466
Received: 22 December 2017 / Revised: 29 January 2018 / Accepted: 2 February 2018 / Published: 5 February 2018
(This article belongs to the Section Biochemistry)
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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MDPI and ACS Style

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. https://doi.org/10.3390/ijms19020466

AMA Style

Kanno H, Xu Y, Miyakawa T, Kubo A, Higashida T, Kobayashi NB, Yoshida T, Tanokura M. BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells. International Journal of Molecular Sciences. 2018; 19(2):466. https://doi.org/10.3390/ijms19020466

Chicago/Turabian Style

Kanno, Hiroshi; Xu, Yuqun; Miyakawa, Taykua; Kubo, Atsuhiko; Higashida, Tetsuhiro; Kobayashi, Nahoko B.; Yoshida, Tetsuhiko; Tanokura, Masaru. 2018. "BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells" Int. J. Mol. Sci. 19, no. 2: 466. https://doi.org/10.3390/ijms19020466

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