SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

Tankou, S. et al. (2016) SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex. Molecular Neuropsychiatry, 2(1), pp. 20-27. (doi:10.1159/000444257)

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Abstract

DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baillie, Professor George and Houslay, Professor Miles and Elliott, Dr Christina and Yalla, Dr Krishna
Authors: Tankou, S., Ishii, K., Elliott, C., Yalla, K., Kubo, K.-i., Brandon, N. J., Tang, Q., Hayward, G., Nakajima, K., Houslay, M., Kamiya, A., Baillie, G., Ishizuka, K., and Sawa, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Molecular Neuropsychiatry
Publisher:Karger
ISSN:2296-9209
ISSN (Online):2296-9179
Published Online:15 March 2016
Copyright Holders:Copyright © 2016 S. Karger AG, Basel
First Published:First published in Molecular Neuropsychiatry 2(1):20-27
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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