PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens

Yoko H. Ohnishi, Yoshinori N. Ohnishi, Takanori Nakamura, Mizuki Ohno, Pamela J. Kennedy, Ohkawa Yasuyuki, Akinori Nishi, Rachael Neve, Teruhisa Tsuzuki, Eric J. Nestler

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

ΔFosB 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 ΔFosB 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 ΔFosB 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 ΔFosB. We verify such interactions between endogenous ΔFosB 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 ΔFosB and, for the first time, implicates PSMC5 in cocaine-induced molecular and behavioral plasticity.

Original languageEnglish
Article numbere0126710
JournalPloS one
Volume10
Issue number5
DOIs
Publication statusPublished - May 11 2015

Fingerprint

cocaine
Nucleus Accumbens
Cocaine
adenosinetriphosphatase
Adenosine Triphosphatases
Brain
brain
Transcription Factors
transcription factors
drug abuse
two hybrid system techniques
Two-Hybrid System Techniques
Proteins
gene activation
regulatory proteins
Street Drugs
chronic exposure
Reward
Yeast
Transcriptional Activation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Ohnishi, Y. H., Ohnishi, Y. N., Nakamura, T., Ohno, M., Kennedy, P. J., Yasuyuki, O., ... Nestler, E. J. (2015). PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens. PloS one, 10(5), [e0126710]. https://doi.org/10.1371/journal.pone.0131263

PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens. / Ohnishi, Yoko H.; Ohnishi, Yoshinori N.; Nakamura, Takanori; Ohno, Mizuki; Kennedy, Pamela J.; Yasuyuki, Ohkawa; Nishi, Akinori; Neve, Rachael; Tsuzuki, Teruhisa; Nestler, Eric J.

In: PloS one, Vol. 10, No. 5, e0126710, 11.05.2015.

Research output: Contribution to journalArticle

Ohnishi, YH, Ohnishi, YN, Nakamura, T, Ohno, M, Kennedy, PJ, Yasuyuki, O, Nishi, A, Neve, R, Tsuzuki, T & Nestler, EJ 2015, 'PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens', PloS one, vol. 10, no. 5, e0126710. https://doi.org/10.1371/journal.pone.0131263
Ohnishi, Yoko H. ; Ohnishi, Yoshinori N. ; Nakamura, Takanori ; Ohno, Mizuki ; Kennedy, Pamela J. ; Yasuyuki, Ohkawa ; Nishi, Akinori ; Neve, Rachael ; Tsuzuki, Teruhisa ; Nestler, Eric J. / PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens. In: PloS one. 2015 ; Vol. 10, No. 5.
@article{6395a8db17a540e3950237cad3b904ea,
title = "PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens",
abstract = "ΔFosB 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 ΔFosB 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 ΔFosB 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 ΔFosB. We verify such interactions between endogenous ΔFosB 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 ΔFosB and, for the first time, implicates PSMC5 in cocaine-induced molecular and behavioral plasticity.",
author = "Ohnishi, {Yoko H.} and Ohnishi, {Yoshinori N.} and Takanori Nakamura and Mizuki Ohno and Kennedy, {Pamela J.} and Ohkawa Yasuyuki and Akinori Nishi and Rachael Neve and Teruhisa Tsuzuki and Nestler, {Eric J.}",
year = "2015",
month = "5",
day = "11",
doi = "10.1371/journal.pone.0131263",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - PSMC5, a 19S proteasomal ATPase, regulates cocaine action in the nucleus accumbens

AU - Ohnishi, Yoko H.

AU - Ohnishi, Yoshinori N.

AU - Nakamura, Takanori

AU - Ohno, Mizuki

AU - Kennedy, Pamela J.

AU - Yasuyuki, Ohkawa

AU - Nishi, Akinori

AU - Neve, Rachael

AU - Tsuzuki, Teruhisa

AU - Nestler, Eric J.

PY - 2015/5/11

Y1 - 2015/5/11

N2 - ΔFosB 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 ΔFosB 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 ΔFosB 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 ΔFosB. We verify such interactions between endogenous ΔFosB 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 ΔFosB and, for the first time, implicates PSMC5 in cocaine-induced molecular and behavioral plasticity.

AB - ΔFosB 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 ΔFosB 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 ΔFosB 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 ΔFosB. We verify such interactions between endogenous ΔFosB 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 ΔFosB and, for the first time, implicates PSMC5 in cocaine-induced molecular and behavioral plasticity.

UR - http://www.scopus.com/inward/record.url?scp=84956692800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956692800&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0131263

DO - 10.1371/journal.pone.0131263

M3 - Article

C2 - 25962134

AN - SCOPUS:84956692800

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e0126710

ER -