-
Something wrong with this record ?
PPM1D activity promotes cellular transformation by preventing senescence and cell death
M. Stoyanov, AS. Martinikova, K. Matejkova, K. Horackova, P. Zemankova, K. Burdova, Z. Zemanova, P. Kleiblova, Z. Kleibl, L. Macurek
Language English Country England, Great Britain
Document type Journal Article
Grant support
NU22-03-00276
Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)
142121
Grantová Agentura, Univerzita Karlova (Charles University Grant Agency)
NLK
ProQuest Central
from 2000-01-01 to 1 year ago
Open Access Digital Library
from 1997-01-01
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-01-01 to 1 year ago
- MeSH
- Cell Death genetics MeSH
- Humans MeSH
- Mice MeSH
- Cell Transformation, Neoplastic * genetics MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- DNA Damage * genetics MeSH
- Cell Proliferation genetics MeSH
- Protein Phosphatase 2C * genetics metabolism MeSH
- Phosphoprotein Phosphatases genetics metabolism MeSH
- Cellular Senescence * genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Cell cycle checkpoints, oncogene-induced senescence and programmed cell death represent intrinsic barriers to tumorigenesis. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of the tumour suppressor p53 and has been implicated in termination of the DNA damage response. Here, we addressed the consequences of increased PPM1D activity resulting from the gain-of-function truncating mutations in exon 6 of the PPM1D. We show that while control cells permanently exit the cell cycle and reside in senescence in the presence of DNA damage caused by ionising radiation or replication stress induced by the active RAS oncogene, RPE1-hTERT and BJ-hTERT cells carrying the truncated PPM1D continue proliferation in the presence of DNA damage, form micronuclei and accumulate genomic rearrangements revealed by karyotyping. Further, we show that increased PPM1D activity promotes cell growth in the soft agar and formation of tumours in xenograft models. Finally, expression profiling of the transformed clones revealed dysregulation of several oncogenic and tumour suppressor pathways. Our data support the oncogenic potential of PPM1D in the context of exposure to ionising radiation and oncogene-induced replication stress.
Department of Cell Biology Faculty of Science Charles University Prague Czech Republic
Department of Genetics and Microbiology Faculty of Science Charles University Prague Czech Republic
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc25004013
- 003
- CZ-PrNML
- 005
- 20250515095622.0
- 007
- ta
- 008
- 250121s2024 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1038/s41388-024-03149-3 $2 doi
- 035 __
- $a (PubMed)39237765
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Stoyanov, Miroslav $u Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic $u Department of Cell Biology, Faculty of Science, Charles University, Prague, Czech Republic $1 https://orcid.org/0000000231599058
- 245 10
- $a PPM1D activity promotes cellular transformation by preventing senescence and cell death / $c M. Stoyanov, AS. Martinikova, K. Matejkova, K. Horackova, P. Zemankova, K. Burdova, Z. Zemanova, P. Kleiblova, Z. Kleibl, L. Macurek
- 520 9_
- $a Cell cycle checkpoints, oncogene-induced senescence and programmed cell death represent intrinsic barriers to tumorigenesis. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of the tumour suppressor p53 and has been implicated in termination of the DNA damage response. Here, we addressed the consequences of increased PPM1D activity resulting from the gain-of-function truncating mutations in exon 6 of the PPM1D. We show that while control cells permanently exit the cell cycle and reside in senescence in the presence of DNA damage caused by ionising radiation or replication stress induced by the active RAS oncogene, RPE1-hTERT and BJ-hTERT cells carrying the truncated PPM1D continue proliferation in the presence of DNA damage, form micronuclei and accumulate genomic rearrangements revealed by karyotyping. Further, we show that increased PPM1D activity promotes cell growth in the soft agar and formation of tumours in xenograft models. Finally, expression profiling of the transformed clones revealed dysregulation of several oncogenic and tumour suppressor pathways. Our data support the oncogenic potential of PPM1D in the context of exposure to ionising radiation and oncogene-induced replication stress.
- 650 12
- $a proteinfosfatasa 2C $x genetika $x metabolismus $7 D000071636
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a stárnutí buněk $x genetika $7 D016922
- 650 12
- $a nádorová transformace buněk $x genetika $7 D002471
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a myši $7 D051379
- 650 12
- $a poškození DNA $x genetika $7 D004249
- 650 _2
- $a proliferace buněk $x genetika $7 D049109
- 650 _2
- $a buněčná smrt $x genetika $7 D016923
- 650 _2
- $a nádorový supresorový protein p53 $x genetika $x metabolismus $7 D016159
- 650 _2
- $a proteinfosfatasy $x genetika $x metabolismus $7 D010749
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Martinikova, Andra S $u Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Matějková, Kateřina, $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic $u Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republic $d 1998- $7 xx0332267
- 700 1_
- $a Horackova, Klara $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Zemankova, Petra $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Burdova, Kamila $u Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Zemanova, Zuzana $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic $1 https://orcid.org/0000000275386601 $7 nlk20050170627
- 700 1_
- $a Kleiblova, Petra $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Kleibl, Zdenek $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic $1 https://orcid.org/0000000320509667 $7 jo2003183974
- 700 1_
- $a Macurek, Libor $u Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic. libor.macurek@img.cas.cz $1 https://orcid.org/0000000209871238 $7 xx0128728
- 773 0_
- $w MED00003600 $t Oncogene $x 1476-5594 $g Roč. 43, č. 42 (2024), s. 3081-3093
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/39237765 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20250121 $b ABA008
- 991 __
- $a 20250515095623 $b ABA008
- 999 __
- $a ok $b bmc $g 2263637 $s 1240020
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 43 $c 42 $d 3081-3093 $e 20240905 $i 1476-5594 $m Oncogene $n Oncogene $x MED00003600
- GRA __
- $a NU22-03-00276 $p Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)
- GRA __
- $a 142121 $p Grantová Agentura, Univerzita Karlova (Charles University Grant Agency)
- LZP __
- $a Pubmed-20250121
