Wip1 PHOSPHATASE AFFECTS SENSITIVITY OF MURINE SKIN CELLS TO UV-B IRRADIATION
Y.Yu. Kochetkova,1 T.V. Pospelova,1 O.N. Demidov 1,2
1 Institute of Cytology RAS, St. Petersburg, 194064, and 2 INSERM UMR866, University of Burgundy, France;
1 e-mail: lena.linnaea@gmail.com
UV irradiation is one of the major natural and artificial stress factors which may cause severe damage to
the skin. UV irradiation induces DNA damage in cells that eventually could lead to cell death, senescence or acquiring
oncogenic mutations and tumor growth. Wip1 is a phosphatase involved in regulation of signaling in
DNA damage response and oncogenic stress. Here we studied response to UV-B irradiation in wild type and
Wip1 depleted murine cells of epidermal and mesenchymal lineages. We found that both cell types, skin keratinocytes
and fibroblasts, respond to UV-B in a similar manner with increased cytotoxicity in Wip1–/– cells. The
number of nuclear foci of Wip1 target protein, DNA damage marker, histone gH2A-X, was highly elevated in
Wip1–/– cells before and after UV-B. We observed two-fold increase in number of cells with active caspase-3
in keratinocytes with Wip1 deletion. Thus, Wip1 deficiency sensitizes cells to UV-B irradiation by promoting
cell death, possibly by caspase-3 dependent apoptosis.
Key words:
UV irradiation, Wip1 knockout mice, keratinocytes, fibroblasts, DNA damage
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