Reference : Hypoxia-inducible Factor-1-dependent Overexpression of Myeloid Cell Factor-1 Protects...
Scientific journals : Article
Human health sciences : Oncology
Hypoxia-inducible Factor-1-dependent Overexpression of Myeloid Cell Factor-1 Protects Hypoxic Cells against tert-Butyl Hydroperoxide-induced Apoptosis
Piret, Jean-Pascal [ > > ]
Minet, Emmanuel [ > > ]
Cosse, Jean-Philippe mailto [Université de Liège - ULiège > > GIGA-R : Epigénétique Cellulaire et Moléculaire >]
Ninane, Noelle [ > > ]
Debacq, Christophe [ > > ]
Raes, Martine [ > > ]
Michiels, Carine [ > > ]
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Yes (verified by ORBi)
[en] Hypoxia ; apoptosis ; Mcl-1 ; HIF-1
[en] Increased levels of Mcl-1 (myeloid cell factor-1) have
been reported in several cancers, suggesting an important
role played by Mcl-1 in cancer cell survival. Mcl-1 is
an anti-apoptotic protein shown to delay or block apoptosis.
In this work, using semiquantitative immunofluorescence,
real-time PCR, and RNase protection assay,
an increase in Mcl-1 expression was detected in hepatoma
HepG2 cells incubated under hypoxia or in the
presence of cobalt chloride. Through analysis of the
Mcl-1 promoter sequence, a putative HIF-1 (hypoxiainducible
factor-1) binding site was identified. A Mcl-1
promoter fragment containing this hypoxia-responsive
element was able to bind HIF-1 in vitro. It also induced
hypoxia-dependent transcription of a luciferase reporter
gene, which was suppressed by anti-HIF-1 short
interfering RNA. Finally, overexpression of Mcl-1 protected
HepG2 cells against apoptosis induced by tertbutyl
hydroperoxide as shown by inhibition of caspase-3
activation and DNA fragmentation. All these data suggest
a potential anti-apoptotic role of HIF-1 that could
protect cells against apoptosis under hypoxia by overexpression
of the Mcl-1 protein.
Unité de Recherche en Biologie Cellulaire
Facultés Universitaires Notre-Dame de La Paix

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