VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU.
- Publisher:
- SPRINGERNATURE
- Publication Type:
- Journal Article
- Citation:
- Cell Death Dis, 2023, 14, (2), pp. 114
- Issue Date:
- 2023-02-13
Open Access
Copyright Clearance Process
- Recently Added
- In Progress
- Open Access
This item is open access.
Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Su, B | |
dc.contributor.author | Lim, D | |
dc.contributor.author | Qi, C | |
dc.contributor.author | Zhang, Z | |
dc.contributor.author | Wang, J | |
dc.contributor.author | Zhang, F | |
dc.contributor.author | Dong, C | |
dc.contributor.author | Feng, Z | |
dc.date.accessioned | 2023-10-05T00:40:02Z | |
dc.date.available | 2023-02-02 | |
dc.date.available | 2023-10-05T00:40:02Z | |
dc.date.issued | 2023-02-13 | |
dc.identifier.citation | Cell Death Dis, 2023, 14, (2), pp. 114 | |
dc.identifier.issn | 2041-4889 | |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | http://hdl.handle.net/10453/172504 | |
dc.description.abstract | Cell cycle checkpoint kinases play a pivotal role in protecting against replicative stress. In this study, valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was found to promote breast cancer MCF-7 cells to traverse into G2/M phase for catastrophic injury by promoting PPP2R2A (the B-regulatory subunit of Phosphatase PP2A) to facilitate the dephosphorylation of Chk1 at Ser317 and Ser345. By contrast, VPA protected normal 16HBE cells from HU toxicity through decreasing PPP2R2A expression and increasing Chk1 phosphorylation. The effect of VPA on PPP2R2A was at the post-transcription level through HDAC1/2. The in vitro results were affirmed in vivo. Patients with lower PPP2R2A expression and higher pChk1 expression showed significantly worse survival. PPP2R2A D197 and N181 are essential for PPP2R2A-Chk1 signaling and VPA-mediated bidirectional effect on augmenting HU-induced tumor cell death and protecting normal cells. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | SPRINGERNATURE | |
dc.relation.ispartof | Cell Death Dis | |
dc.relation.isbasedon | 10.1038/s41419-023-05649-8 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 0601 Biochemistry and Cell Biology, 1112 Oncology and Carcinogenesis | |
dc.subject.classification | 3101 Biochemistry and cell biology | |
dc.subject.classification | 3211 Oncology and carcinogenesis | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Valproic Acid | |
dc.subject.mesh | Cell Division | |
dc.subject.mesh | Phosphorylation | |
dc.subject.mesh | Histone Deacetylase Inhibitors | |
dc.subject.mesh | DNA Replication | |
dc.subject.mesh | Cell Cycle | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Protein Phosphatase 2 | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Valproic Acid | |
dc.subject.mesh | Cell Cycle | |
dc.subject.mesh | Cell Division | |
dc.subject.mesh | DNA Replication | |
dc.subject.mesh | Phosphorylation | |
dc.subject.mesh | Protein Phosphatase 2 | |
dc.subject.mesh | Histone Deacetylase Inhibitors | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Valproic Acid | |
dc.subject.mesh | Cell Division | |
dc.subject.mesh | Phosphorylation | |
dc.subject.mesh | Histone Deacetylase Inhibitors | |
dc.subject.mesh | DNA Replication | |
dc.subject.mesh | Cell Cycle | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Protein Phosphatase 2 | |
dc.title | VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU. | |
dc.type | Journal Article | |
utslib.citation.volume | 14 | |
utslib.location.activity | England | |
utslib.for | 0601 Biochemistry and Cell Biology | |
utslib.for | 1112 Oncology and Carcinogenesis | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Health | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Health/IMPACCT | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2023-10-05T00:39:51Z | |
pubs.issue | 2 | |
pubs.publication-status | Published online | |
pubs.volume | 14 | |
utslib.citation.issue | 2 |
Abstract:
Cell cycle checkpoint kinases play a pivotal role in protecting against replicative stress. In this study, valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was found to promote breast cancer MCF-7 cells to traverse into G2/M phase for catastrophic injury by promoting PPP2R2A (the B-regulatory subunit of Phosphatase PP2A) to facilitate the dephosphorylation of Chk1 at Ser317 and Ser345. By contrast, VPA protected normal 16HBE cells from HU toxicity through decreasing PPP2R2A expression and increasing Chk1 phosphorylation. The effect of VPA on PPP2R2A was at the post-transcription level through HDAC1/2. The in vitro results were affirmed in vivo. Patients with lower PPP2R2A expression and higher pChk1 expression showed significantly worse survival. PPP2R2A D197 and N181 are essential for PPP2R2A-Chk1 signaling and VPA-mediated bidirectional effect on augmenting HU-induced tumor cell death and protecting normal cells.
Please use this identifier to cite or link to this item:
Download statistics for the last 12 months
Not enough data to produce graph