Fu Cheng, Chen Dong, Chen Ruijie, Hu Qingsong, Wang Guanghui
Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Diseases and School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences. Hefei, Anhui, China.
Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
PLoS One. 2015 Jul 14;10(7):e0132639. doi: 10.1371/journal.pone.0132639. eCollection 2015.
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.
肌萎缩蛋白结合蛋白1（DTNBP1）是一种编码肌萎缩蛋白-1的基因，已被确定为精神分裂症的易感基因。该基因与突触或细胞质中的伙伴协同作用，调节神经突生长和神经递质释放。肌萎缩蛋白-1的缺失会影响精神分裂症的病理过程。然而，在细胞核中也发现了肌萎缩蛋白-1，但其在细胞核中的特性尚未完全明确。在此，我们发现肌萎缩蛋白-1A在细胞核中通过泛素-蛋白酶体系统降解，并且该过程需要N端的2至41位氨基酸。通过与p65相互作用，肌萎缩蛋白-1A促进细胞核中NF-κB的转录活性，并正向调节MMP-9的表达。综上所述，本研究获得的数据表明，肌萎缩蛋白-1A的蛋白水平在细胞核中受到高度调控，并且肌萎缩蛋白-1A调节转录因子NF-κB的活性，以促进MMP-9和TNF-α的表达。
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