| First Author | Ohnishi YH | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 5 | Pages | e0126710 |
| PubMed ID | 25962134 | Mgi Jnum | J:235333 |
| Mgi Id | MGI:5796090 | Doi | 10.1371/journal.pone.0126710 |
| Citation | Ohnishi YH, et al. (2015) PSMC5, a 19S Proteasomal ATPase, Regulates Cocaine Action in the Nucleus Accumbens. PLoS One 10(5):e0126710 |
| abstractText | DeltaFosB is a stable transcription factor which accumulates in the nucleus accumbens (NAc), a key part of the brain's reward circuitry, in response to chronic exposure to cocaine or other drugs of abuse. While DeltaFosB is known to heterodimerize with a Jun family member to form an active transcription factor complex, there has not to date been an open-ended exploration of other possible binding partners for DeltaFosB in the brain. Here, by use of yeast two-hybrid assays, we identify PSMC5-also known as SUG1, an ATPase-containing subunit of the 19S proteasomal complex-as a novel interacting protein with DeltaFosB. We verify such interactions between endogenous DeltaFosB and PSMC5 in the NAc and demonstrate that both proteins also form complexes with other chromatin regulatory proteins associated with gene activation. We go on to show that chronic cocaine increases nuclear, but not cytoplasmic, levels of PSMC5 in the NAc and that overexpression of PSMC5 in this brain region promotes the locomotor responses to cocaine. Together, these findings describe a novel mechanism that contributes to the actions of DeltaFosB and, for the first time, implicates PSMC5 in cocaine-induced molecular and behavioral plasticity. |
