Article (Scientific journals)
Melanoma antigen-D2 controls cell cycle progression and modulates the DNA damage response.
Trussart, Charlotte; Pirlot, Céline; Di Valentin, Emmanuel et al.
2018In Biochemical Pharmacology
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Keywords :
MAGED2; cell cycle; SKP2; Camptothecin; ATR
Abstract :
[en] Overexpression of the ubiquitous type II melanoma antigen-D2 (MAGED2) in numerous types of cancer suggests that this protein contributes to carcinogenesis, a well-documented characteristic of other MAGE proteins. Modification of MAGED2 intracellular localization during cell cycle phases and following treatment with camptothecin (CPT) and phosphorylation by ATM/ATR following ionizing irradiation led us to investigate the molecular functions of MAGED2 in the cellular response to DNA damage. Cell cycle regulators, cell cycle progression, and bromodeoxyuridine (BrdU) incorporation were compared between MAGED2-sufficient and -depleted U2OS cells following exposure to CPT. At 24 h post-CPT removal, MAGED2-depleted cells had lower levels of p21 and p27, and there was an increase in S phase BrdU-positive cells with a concurrent decrease in cells in G2. These cell cycle modifications were p21-independent, but ATR-, SKP2-, and CDC20-dependent. Importantly, while MAGED2 depletion reduced CHK2 phosphorylation after 8 h of CPT treatment, it enhanced and prolonged CHK1 phosphorylation after a 24 h recovery period, indicating sustained ATR activation. MAGED2 depletion had no impact on cell survival under our experimental conditions. In summary, our data indicate that MAGED2 reduced CPT-related replicative stress, suggesting a role for this protein in genomic stability.
Research center :
GIGA Molecular Biology of Diseases - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Trussart, Charlotte ;  Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Pirlot, Céline
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Habraken, Yvette ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Language :
English
Title :
Melanoma antigen-D2 controls cell cycle progression and modulates the DNA damage response.
Publication date :
2018
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier, Netherlands
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
Fonds Léon Fredericq [BE]
CAC - Centre anticancéreux près l'Université de Liège asbl [BE]
IAP7
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