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Papers In Press, published online ahead of print June 17, 2002
Department of Dermatology, Katholieke Universiteit Leuven, Leuven B-3000
Corresponding Author: Marjan.Garmyn{at}med.kuleuven.ac.be
Insulin-like growth factor 1 (IGF-1) acts as a potent survival factor in numerous cell lines, primarily through activation of the AKT signaling pathway. Although some targets of this pathway have known anti-apoptotic functions, its relationship with the improved survival of cells after exposure to environmental stresses, including UVB, remains largely unclear. We report that in growth factor-deprived keratinocytes, IGF-1 significantly and consistently delays the onset of UVB-induced apoptosis by more than 7 hours. This delay allows IGF-1 supplemented keratinocytes to repair significantly more cyclobutane thymine dimers than their growth factor-deprived counterparts. This increase in cyclobutane thymine removal results in an enhanced survival if the amount of DNA damage is not too high. In order to increase cellular survival after UVB-irradiation, IGF-1 supplementation is only required during this initial time period in which extra repair is executed. Finally we show that IGF-1 mediates this delay of the onset of UVB-induced apoptosis through activation of the AKT signaling pathway. We therefore believe that the Akt signaling pathway increases cellular survival after a genotoxic insult such as UVB-irradiation, not by inhibiting the apoptotic stimulus, but only by postponing the induction of apoptosis, giving the DNA repair mechanism more time to work.
J. Biol. Chem, 10.1074/jbc.M111106200
Submitted on November 20, 2001
Revised on May 14, 2002
Accepted on June 17, 2002
IGF-1 mediated AKT activation postpones the onset of UVB-induced apoptosis, providing more time for cyclobutane thymine dimer removal in primary human keratinocytes
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