Lysine-Less Variants of Spinal Muscular Atrophy SMN and SMNΔ7 Proteins Are Degraded by the Proteasome Pathway

Sánchez-Lanzas, Raúl; Castaño, José G.

doi:10.3390/ijms18122667

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Lysine-Less Variants of Spinal Muscular Atrophy SMN and SMNΔ7 Proteins Are Degraded by the Proteasome Pathway

Raúl Sánchez-Lanzas

and

José G. Castaño

Departamento de Bioquímica, Instituto de Investigaciones Biomédicas “Alberto Sols” (UAM-CSIC), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2017, 18(12), 2667; https://doi.org/10.3390/ijms18122667

Received: 20 October 2017 / Revised: 30 November 2017 / Accepted: 4 December 2017 / Published: 8 December 2017

(This article belongs to the Special Issue Ubiquitin System)

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Abstract

Spinal muscular atrophy is due to mutations affecting the SMN1 gene coding for the full-length protein (survival motor neuron; SMN) and the SMN2 gene that preferentially generates an exon 7-deleted protein (SMNΔ7) by alternative splicing. To study SMN and SMNΔ7 degradation in the cell, we have used tagged versions at the N- (Flag) or C-terminus (V5) of both proteins. Transfection of those constructs into HeLa cells and treatment with cycloheximide showed that those protein constructs were degraded. Proteasomal degradation usually requires prior lysine ubiquitylation. Surprisingly, lysine-less variants of both proteins tagged either at N- (Flag) or C-terminus (V5) were also degraded. The degradation of the endogenous SMN protein, and the protein constructs mentioned above, was mediated by the proteasome, as it was blocked by lactacystin, a specific and irreversible proteasomal inhibitor. The results obtained allowed us to conclude that SMN and SMNΔ7 proteasomal degradation did not absolutely require internal ubiquitylation nor N-terminal ubiquitylation (prevented by N-terminal tagging). While the above conclusions are firmly supported by the experimental data presented, we discuss and justify the need of deep proteomic techniques for the study of SMN complex components (orphan and bound) turn-over to understand the physiological relevant mechanisms of degradation of SMN and SMNΔ7 in the cell. View Full-Text

Keywords: survival motor neuron (SMN); ubiquitin; proteasome; protein degradation discipline

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Sánchez-Lanzas, R.; Castaño, J.G. Lysine-Less Variants of Spinal Muscular Atrophy SMN and SMNΔ7 Proteins Are Degraded by the Proteasome Pathway. Int. J. Mol. Sci. 2017, 18, 2667. https://doi.org/10.3390/ijms18122667

AMA Style

Sánchez-Lanzas R, Castaño JG. Lysine-Less Variants of Spinal Muscular Atrophy SMN and SMNΔ7 Proteins Are Degraded by the Proteasome Pathway. International Journal of Molecular Sciences. 2017; 18(12):2667. https://doi.org/10.3390/ijms18122667

Chicago/Turabian Style

Sánchez-Lanzas, Raúl, and José G. Castaño. 2017. "Lysine-Less Variants of Spinal Muscular Atrophy SMN and SMNΔ7 Proteins Are Degraded by the Proteasome Pathway" International Journal of Molecular Sciences 18, no. 12: 2667. https://doi.org/10.3390/ijms18122667

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Lysine-Less Variants of Spinal Muscular Atrophy SMN and SMNΔ7 Proteins Are Degraded by the Proteasome Pathway

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