DISC1 as a hub gene FIGURE

This was intended as a support to an online debate in the Schizophrenia Forum Live discussion

The DISC1 primary interactions are from various two-hybrid and other studies (Camargo et al. 2007;Assmann et al. 2006;Miyoshi et al. 2004;Miyoshi et al. 2003;Millar et al. 2003;Morris et al. 2003;Ozeki et al. 2003;Shinoda et al. 2007). Please excuse any omissions.

The subsequent interactions of the DISC1 binding partners are essentially a summary of those found in the ENTREZ Gene interaction section. In some browsers, you should be able to click on the gene to reach this information (This works in Internet explorer but not in Firefox).

Several protein products of genes associated with schizophrenia or bipolar disorder can be directly linked to DISC1 (red lines) while others can be linked in two steps (orange lines).

Red genes have been associated with schizophrenia, yellow genes with bipolar disorder and orange genes with both conditions.

DISC1 PUBMED

Reference List

Assmann E. M., Alborghetti M. R., Camargo M. E., and Kobarg J. (2006) FEZ1 dimerization and interaction with transcription regulatory proteins involves its coiled-coil region. J Biol Chem 281, 9869-9881.

Camargo L. M., Collura V., Rain J. C., Mizuguchi K., Hermjakob H., Kerrien S., Bonnert T. P., Whiting P. J., and Brandon N. J. (2007) Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol Psychiatry 12, 74-86.

Millar J. K., Christie S., and Porteous D. J. (2003) Yeast two-hybrid screens implicate DISC1 in brain development and function. Biochem Biophys Res Commun 311, 1019-1025.

Miyoshi K., Asanuma M., Miyazaki I., Diaz-Corrales F. J., Katayama T., Tohyama M., and Ogawa N. (2004) DISC1 localizes to the centrosome by binding to kendrin. Biochem Biophys Res Commun 317, 1195-1199.

Miyoshi K., Honda A., Baba K., Taniguchi M., Oono K., Fujita T., Kuroda S., Katayama T., and Tohyama M. (2003) Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. Mol Psychiatry 8, 685-694.

Morris J. A., Kandpal G., Ma L., and Austin C. P. (2003) DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Hum Mol Genet 12, 1591-1608.

Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., Okawa M., Yamada N., Hatten M. E., Snyder S. H., Ross C. A., and Sawa A. (2003) Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Proc Natl Acad Sci U S A 100, 289-294.

Shinoda T., Taya S., Tsuboi D., Hikita T., Matsuzawa R., Kuroda S., Iwamatsu A., and Kaibuchi K. (2007) DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. J Neurosci 27, 4-14.