Dendritic cell nuclear protein-1, a novel depression-related protein, upregulates corticotropin-releasing hormone expression.
The recently discovered dendritic cell nuclear protein-1 is the product of a novel candidate gene for major depression. The A allele encodes full-length dendritic cell nuclear protein-1, while the T allele encodes a premature termination of translation at codon number 117 on chromosome 5. In the present study we investigate whether the two forms of dendritic cell nuclear protein-1 might act on corticotropin-releasing hormone, which plays a crucial role in the stress response and in the pathogenesis of depression. The messenger RNA expression of dendritic cell nuclear protein-1 appeared to be increased in the laser micro-dissected paraventricular nucleus of patients with depression compared with control subjects. Dendritic cell nuclear protein-1 was also found to be co-localized with corticotropin-releasing hormone in paraventricular nucleus neurons. Moreover, full-length dendritic cell nucleus protein-1 bound to and transactivated the promoter of corticotropin-releasing hormone in human embryonic kidney 293 cells. We propose that full-length dendritic cell nucleus protein-1 may play a role in the pathogenesis of depressive disorders by enhancing corticotropin-releasing hormone expression in the hypothalamic paraventricular nucleus.
Zhou
Tian
T
Netherlands Institute for Neuroscience, Meibergdreef 47, Amsterdam, The Netherlands.
Wang
Shanshan
S
Ren
Haigang
H
Qi
Xin-Rui
XR
Luchetti
Sabina
S
Kamphuis
Willem
W
Zhou
Jiang-Ning
JN
Wang
Guanghui
G
Swaab
Dick F
DF
D001921:Brain / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D042282:Microdissection / Q000379:methods; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D015854:Up-Regulation
C446761:DCANP1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone