TY  - JOUR
AU  - Yerabham, Antony S. K.
AU  - Weiergräber, Oliver H.
AU  - Bradshaw, Nicholas J.
AU  - Korth, Carsten
TI  - Revisiting Disrupted-in-Schizophrenia 1 as a scaffold protein
JO  - Biological chemistry
VL  - 394
IS  - 11
SN  - 1437-4315
CY  - Berlin [u.a.]
PB  - de Gruyter
M1  - FZJ-2013-05122
SP  - 1425-1437
PY  - 2013
AB  - Disrupted-in-Schizophrenia 1 (DISC1) is a widely-accepted genetic risk factor for schizophrenia and many other major mental illnesses. Traditionally DISC1 has been referred to as a ‘scaffold protein’ because of its ability to bind to a wide array of other proteins, including those of importance for neurodevelopment. Here, we review the characteristic properties shared between established scaffold proteins and DISC1. We find DISC1 to have many, but not all, of the characteristics of a scaffold protein, as it affects a considerable number of different, but related, signaling pathways, in most cases through inhibition of key enzymes. Using threading algorithms, the C-terminal portion of DISC1 could be mapped to extended helical structures, yet it may not closely resemble any of the known tertiary folds. While not completely fitting the classification of a classical scaffold protein, DISC1 does appear to be a tightly regulated and multi-faceted inhibitor of a wide range of enzymes from interrelated signaling cascades (Diverse Inhibitor of Signaling Cascades), which together contribute to neurodevelopment and synaptic homeostasis. Consequently, disruption of this complex regulation would be expected to lead to the range of major mental illnesses in which the DISC1 gene has been implicated.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000325717100007
DO  - DOI:10.1515/hsz-2013-0178
UR  - https://juser.fz-juelich.de/record/139115
ER  -