| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 36, 32587-32595, September 6, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the 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 delayed the onset of UVB-induced apoptosis by >7 h. This delay allowed IGF-1-supplemented keratinocytes to repair significantly more
cyclobutane thymine dimers than their growth factor-deprived counterparts. This increase in cyclobutane thymine removal resulted in
enhanced survival if the amount of DNA damage was not too high. To
increase cell survival after UVB irradiation, IGF-1 supplementation was
required only during this initial time period in which extra repair was
executed. Finally, we show that IGF-1 mediated this delay in the onset
of UVB-induced apoptosis through activation of the AKT signaling
pathway. We therefore believe that the AKT signaling pathway increases
cell 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.
Insulin-like Growth Factor-1-mediated AKT Activation Postpones
the Onset of Ultraviolet B-induced Apoptosis, Providing More Time
for Cyclobutane Thymine Dimer Removal in Primary Human
Keratinocytes*
,, and
Department of Dermatology, the
§ Division of Biochemistry, and the ¶ Laboratory for
Experimental Medicine and Endocrinology, Faculty of Medicine,
Katholieke Universiteit, B-3000 Leuven, Belgium
*
This work was supported in part by Grant OT/00/33 from the
University of Leuven and Grant 0211.99 from the Fonds voor
Wetenschappelijk Onderzoek-Vlaanderen, Belgium.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Dermatology, UZ St. Rafaël, Kapucijnenvoer 33, B-3000 Leuven,
Belgium. Tel.: 32-16-346183; Fax: 32-16-346278; E-mail:
Marjan.Garmyn@med.kuleuven.ac.be.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Chi-Hang Li and R. Li RAV12 Accelerates the Desensitization of Akt/PKB Pathway of Insulin-like Growth Factor I Receptor Signaling in COLO205 Cancer Res., September 15, 2007; 67(18): 8856 - 8864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Crowell, V. E. Steele, and J. R. Fay Targeting the AKT protein kinase for cancer chemoprevention Mol. Cancer Ther., August 1, 2007; 6(8): 2139 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rasoulpour, K. DiPalma, B. Kolvek, and M. Hixon Akt1 Suppresses Radiation-Induced Germ Cell Apoptosis in Vivo Endocrinology, September 1, 2006; 147(9): 4213 - 4221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kadekaro, R. Kavanagh, H. Kanto, S. Terzieva, J. Hauser, N. Kobayashi, S. Schwemberger, J. Cornelius, G. Babcock, H. G. Shertzer, et al. {alpha}-Melanocortin and Endothelin-1 Activate Antiapoptotic Pathways and Reduce DNA Damage in Human Melanocytes Cancer Res., May 15, 2005; 65(10): 4292 - 4299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bohm, I. Wolff, T. E. Scholzen, S. J. Robinson, E. Healy, T. A. Luger, T. Schwarz, and A. Schwarz {alpha}-Melanocyte-stimulating Hormone Protects from Ultraviolet Radiation-induced Apoptosis and DNA Damage J. Biol. Chem., February 18, 2005; 280(7): 5795 - 5802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Tu, T. Melendy, and T. A. Beerman DNA damage responses triggered by a highly cytotoxic monofunctional DNA alkylator, hedamycin, a pluramycin antitumor antibiotic Mol. Cancer Ther., May 1, 2004; 3(5): 577 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Trojanek, T. Ho, L. Del Valle, M. Nowicki, J. Y. Wang, A. Lassak, F. Peruzzi, K. Khalili, T. Skorski, and K. Reiss Role of the Insulin-Like Growth Factor I/Insulin Receptor Substrate 1 Axis in Rad51 Trafficking and DNA Repair by Homologous Recombination Mol. Cell. Biol., November 1, 2003; 23(21): 7510 - 7524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-D. Oh and J.-S. Chun Signaling Mechanisms Leading to the Regulation of Differentiation and Apoptosis of Articular Chondrocytes by Insulin-like Growth Factor-1 J. Biol. Chem., September 19, 2003; 278(38): 36563 - 36571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Girnita, A. Girnita, and O. Larsson Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor PNAS, July 8, 2003; 100(14): 8247 - 8252. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
