AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells.
The protein kinase GSK-3 is constitutively active in quiescent cells in the absence of growth factor signaling. Previously, we identified a set of genes that required GSK-3 to maintain their repression during quiescence. Computational analysis of the upstream sequences of these genes predicted trans...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3102068?pdf=render |
| _version_ | 1818233408731480064 |
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| author | John W Tullai Silvia Tacheva Laura J Owens Julie R Graham Geoffrey M Cooper |
| author_facet | John W Tullai Silvia Tacheva Laura J Owens Julie R Graham Geoffrey M Cooper |
| author_sort | John W Tullai |
| collection | DOAJ |
| description | The protein kinase GSK-3 is constitutively active in quiescent cells in the absence of growth factor signaling. Previously, we identified a set of genes that required GSK-3 to maintain their repression during quiescence. Computational analysis of the upstream sequences of these genes predicted transcription factor binding sites for CREB, NFκB and AP-1. In our previous work, contributions of CREB and NFκB were examined. In the current study, the AP-1 component of the signaling network in quiescent cells was explored.Using chromatin immunoprecipitation analysis, two AP-1 family members, c-Jun and JunD, bound to predicted upstream regulatory sequences in 8 of the 12 GSK-3-regulated genes. c-Jun was phosphorylated on threonine 239 by GSK-3 in quiescent cells, consistent with previous studies demonstrating inhibition of c-Jun by GSK-3. Inhibition of GSK-3 attenuated this phosphorylation, resulting in the stabilization of c-Jun. The association of c-Jun with its target sequences was increased by growth factor stimulation as well as by direct GSK-3 inhibition. The physiological role for c-Jun was also confirmed by siRNA inhibition of gene induction.These results indicate that inhibition of c-Jun by GSK-3 contributes to the repression of growth factor-inducible genes in quiescent cells. Together, AP-1, CREB and NFκB form an integrated transcriptional network that is largely responsible for maintaining repression of target genes downstream of GSK-3 signaling. |
| first_indexed | 2024-12-12T11:21:43Z |
| format | Article |
| id | doaj.art-630d80ebbea1492d817c7b4b3b07c1b2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T11:21:43Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-630d80ebbea1492d817c7b4b3b07c1b22022-12-22T00:26:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e2015010.1371/journal.pone.0020150AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells.John W TullaiSilvia TachevaLaura J OwensJulie R GrahamGeoffrey M CooperThe protein kinase GSK-3 is constitutively active in quiescent cells in the absence of growth factor signaling. Previously, we identified a set of genes that required GSK-3 to maintain their repression during quiescence. Computational analysis of the upstream sequences of these genes predicted transcription factor binding sites for CREB, NFκB and AP-1. In our previous work, contributions of CREB and NFκB were examined. In the current study, the AP-1 component of the signaling network in quiescent cells was explored.Using chromatin immunoprecipitation analysis, two AP-1 family members, c-Jun and JunD, bound to predicted upstream regulatory sequences in 8 of the 12 GSK-3-regulated genes. c-Jun was phosphorylated on threonine 239 by GSK-3 in quiescent cells, consistent with previous studies demonstrating inhibition of c-Jun by GSK-3. Inhibition of GSK-3 attenuated this phosphorylation, resulting in the stabilization of c-Jun. The association of c-Jun with its target sequences was increased by growth factor stimulation as well as by direct GSK-3 inhibition. The physiological role for c-Jun was also confirmed by siRNA inhibition of gene induction.These results indicate that inhibition of c-Jun by GSK-3 contributes to the repression of growth factor-inducible genes in quiescent cells. Together, AP-1, CREB and NFκB form an integrated transcriptional network that is largely responsible for maintaining repression of target genes downstream of GSK-3 signaling.http://europepmc.org/articles/PMC3102068?pdf=render |
| spellingShingle | John W Tullai Silvia Tacheva Laura J Owens Julie R Graham Geoffrey M Cooper AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells. PLoS ONE |
| title | AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells. |
| title_full | AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells. |
| title_fullStr | AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells. |
| title_full_unstemmed | AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells. |
| title_short | AP-1 is a component of the transcriptional network regulated by GSK-3 in quiescent cells. |
| title_sort | ap 1 is a component of the transcriptional network regulated by gsk 3 in quiescent cells |
| url | http://europepmc.org/articles/PMC3102068?pdf=render |
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