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Oncotarget. 2016 Nov 15;7(46):74435-74447. doi: 10.18632/oncotarget.12908.

Absence of ERK5/MAPK7 delays tumorigenesis in Atm-/- mice.

Author information

1
Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
2
Servei d'Anatomia Patològica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Abstract

Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm-/- mice. Compared with Atm-/- thymocytes, Mapk7-/-Atm-/- thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm-/- mice by partially restoring the DNA damage response in thymocytes.

KEYWORDS:

BMK1; DNA damage response; thymic lymphoma; thymocyte; γH2AX

Comment in

PMID:
27793024
PMCID:
PMC5342677
DOI:
10.18632/oncotarget.12908
[Indexed for MEDLINE]
Free PMC Article

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