Melanoma antigen-D2 controls cell cycle progression and modulates the DNA damage response.

[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

Available on ORBi :

since 14 February 2018

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