Title: AKT Delays the Early-Activated Apoptotic Pathway in UVB-Irradiated Keratinocytes Via BAD Translocation
Authors: Claerhout, Sofie ×
Decraene, David
Van Laethem, An
Van Kelst, Sofie
Agostinis, Patrizia
Garmyn, Maria #
Issue Date: Feb-2007
Publisher: Elsevier Science Pub. Co.
Series Title: Journal of Investigative Dermatology vol:127 pages:429-38
Abstract: Upon irradiation with a high dose of UVB, keratinocytes undergo apoptosis as a protective mechanism. In previous work, we demonstrated the existence of an early-activated UVB-induced apoptotic pathway in growth factor-depleted human keratinocytes, which can be substantially delayed by the exclusive supplementation of IGF-1. We now show that in human keratinocytes, IGF-1 inhibits the onset of UVB-triggered apoptosis through a transcriptional independent, AKT-mediated mechanism, involving BAD serine 136 phosphorylation. Our results show that the early UVB-induced apoptosis in growth factor-depleted human keratinocytes is exclusively triggered through the mitochondrial pathway. It is accompanied by BAX translocation, cytochrome c release, and procaspase-9 cleavage, but not by procaspase-8 or BID cleavage. In human keratinocytes, IGF-1 supplementation inhibits these events in a transcription-independent manner. Both IGF-1 supplementation and the transduction of a membrane-targeted form of AKT result in a shift of the BH3-only protein BAD from the mitochondria to the cytoplasm, paralleled by an increase of AKT-specific Ser136 phospho-BAD bound to 14-3-3zeta protein. These data indicate that AKT-induced BAD phosphorylation and its subsequent cytoplasmic sequestration by 14-3-3zeta is a major mechanism responsible for the postponement of UVB-induced apoptosis in human keratinocytes.Journal of Investigative Dermatology advance online publication, 24 August 2006; doi:10.1038/sj.jid.5700533.
ISSN: 0022-202X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Dermatology
Biochemistry Section (Medicine) (-)
Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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