The Schizophrenia-Related Protein Dysbindin-1A Is Degraded and Facilitates NF-Kappa B Activity in the Nucleus.

Abstract

Dystrobrevin-binding protein 1 (DTNBP1), a gene encoding dysbindin-1, has been identified as a susceptibility gene for schizophrenia. Functioning with partners in synapses or the cytoplasm, this gene regulates neurite outgrowth and neurotransmitter release. Loss of dysbindin-1 affects schizophrenia pathology. Dysbindin-1 is also found in the nucleus, however, the characteristics of dysbindin in the nucleus are not fully understood. Here, we found that dysbindin-1A is degraded in the nucleus via the ubiquitin-proteasome system and that amino acids 2-41 at the N-terminus are required for this process. By interacting with p65, dysbindin-1A promotes the transcriptional activity of NF-kappa B in the nucleus and positively regulates MMP-9 expression. Taken together, the data obtained in this study demonstrate that dysbindin-1A protein levels are highly regulated in the nucleus and that dysbindin-1A regulates transcription factor NF-kappa B activity to promote the expression of MMP-9 and TNF-α.

• Authors: Cheng Fu, Dong Chen, Ruijie Chen, Qingsong Hu, Guanghui Wang
• Journal: PloS one (PLoS One) Vol. 10 Issue 7 Pg. e0132639 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26171858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DTNBP1 protein, human
• Dysbindin
• Dystrophin-Associated Proteins
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Ubiquitin
• Matrix Metalloproteinase 9
• Proteasome Endopeptidase Complex

Topics

• Cell Nucleus (metabolism)
• Dysbindin
• Dystrophin-Associated Proteins (chemistry, metabolism)
• Gene Expression Regulation, Enzymologic
• HEK293 Cells
• Humans
• Matrix Metalloproteinase 9 (genetics)
• NF-kappa B (genetics, metabolism)
• Proteasome Endopeptidase Complex (metabolism)
• Proteolysis
• Schizophrenia (metabolism)
• Transcription, Genetic
• Tumor Necrosis Factor-alpha (genetics)
• Ubiquitin (metabolism)