title: SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex.
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 theDISC1gene manifest depression, schizophrenia, and related mental conditions. The discrepancy of modest evidence in genetics but 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 the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where 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 usingin 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.
authors.affiliation: Department of Psychiatry, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tankou
authors.affiliation: Department of Psychiatry, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Molecular Pharmacology Group, CMVLS, University of Glasgow, Glasgow, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Elliott
authors.affiliation: Molecular Pharmacology Group, CMVLS, University of Glasgow, Glasgow, UK.
authors.forename: Krishna C
authors.initials: KC
authors.lastname: Yalla
authors.affiliation: Molecular Pharmacology Group, CMVLS, University of Glasgow, Glasgow, UK.
authors.forename: Jon P
authors.initials: JP
authors.lastname: Day
authors.affiliation: Department of Psychiatry, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukori
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Kubo
authors.affiliation: AstraZeneca Neuroscience iMED, Cambridge, MA, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Brandon
authors.affiliation: Department of Microbiology, Howard University College of Medicine, Washington, DC, USA.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Hayward
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Institute of Pharmaceutical Sciences, King's College London, London, UK.
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
authors.affiliation: Department of Psychiatry, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamiya
authors.affiliation: Molecular Pharmacology Group, CMVLS, University of Glasgow, Glasgow, UK.
authors.forename: George
authors.initials: G
authors.lastname: Baillie
authors.affiliation: Department of Psychiatry, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Koko
authors.initials: K
authors.lastname: Ishizuka
authors.affiliation: Department of Psychiatry, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
keywords: DISC1; SUMOylation; cortical development; mental illness; post-translational modification