Format

Send to

Choose Destination
Biochem Pharmacol. 2018 Jul;153:217-229. doi: 10.1016/j.bcp.2018.01.035. Epub 2018 Feb 1.

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

Author information

1
GIGA-Molecular Biology of Diseases, Virology and Immunology Unit, University of Liège, Quartier de l'Hôpital, 11 Allée de l'Hôpital, Building B34, 4000 Liège, Belgium.
2
GIGA-Viral Vector Platform, University of Liège, Quartier de l'Hôpital, 11 Allée de l'Hôpital, Building B34, 4000 Liège, Belgium.
3
GIGA-Molecular Biology of Diseases, Virology and Immunology Unit, University of Liège, Quartier de l'Hôpital, 11 Allée de l'Hôpital, Building B34, 4000 Liège, Belgium. Electronic address: yvette.habraken@uliege.be.

Abstract

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.

KEYWORDS:

ATR signaling; Camptothecin; S phase; SKP2; melanoma antigen-D2

PMID:
29371029
DOI:
10.1016/j.bcp.2018.01.035
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center