Down-regulation of procaspase-8 expression by focal adhesion kinase protects HL-60 cells from TRAIL-induced apoptosis

Biochemical and Biophysical Research Communications
Yuji TamagikuTadashi Kasahara

Abstract

We have demonstrated that focal adhesion kinase (FAK)-overexpressed (HL-60/FAK) cells have marked resistance against various apoptotic stimuli such as hydrogen peroxide, etoposide, and ionizing radiation compared with the vector-transfected (HL-60/Vect) cells. HL-60/FAK cells are highly resistant to TRAIL-induced apoptosis, while original HL-60 or HL-60/Vect cells were sensitive. TRAIL at 500 ng/ml induced significant DNA fragmentation, activation of caspase-8 and 3, the processing of a proapoptotic BID, and mitochondrial release of cytochrome c in HL-60/Vect cells, whereas no such events were observed in the HL-60/FAK cells. In particular, the expression of procaspase-8 gene and subsequent cleavage of caspase-8 were markedly reduced in HL-60/FAK cells, while expression of TRAIL-receptor 2 and 3, TRADD, and FADD was equivalent in both types of cells. In HL-60/FAK cells, the phosphoinositide 3 (PI3)-kinase/Akt survival pathway was constitutively activated, accompanied by significant induction of inhibitor-of-apoptosis proteins, XIAP, RIP, and Bcl-XL. The introduction of FAK siRNA in HL-60/FAK cells sensitized them against TRAIL-induced apoptosis, confirming that overexpressed FAK downregulates procaspase-8 expression, which subs...Continue Reading

References

May 31, 1996·The Journal of Biological Chemistry·R M PittiA Ashkenazi
Feb 21, 1998·Current Biology : CB·S A MarstersA Ashkenazi
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Jul 20, 2001·The Journal of Biological Chemistry·H ThakkarR K Srivastava
Oct 5, 2001·The Journal of Biological Chemistry·F C KischkelA Ashkenazi
Nov 10, 2001·Trends in Biochemical Sciences·D P Brazil, B A Hemmings
Mar 8, 2002·Cellular Signalling·Karleen M Nicholson, Neil G Anderson
Sep 7, 2002·Antioxidants & Redox Signaling·Tadashi KasaharaYoshiko Sonoda
May 16, 2003·The Journal of Biological Chemistry·Megumi Funakoshi-TagoTadashi Kasahara
Jul 2, 2003·The Journal of Biological Chemistry·Srinivasa M SrinivasulaEmad S Alnemri
Dec 3, 2003·The Journal of Biological Chemistry·Han C DanJin Q Cheng
Mar 23, 2004·Annals of the New York Academy of Sciences·Annick Mühlethaler-MottetNicole Gross
May 4, 2004·Molecular and Cellular Biology·Elena KurenovaWilliam G Cance
Nov 29, 2005·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Y H SoungS H Lee
Aug 15, 2012·Integrative Biology : Quantitative Biosciences From Nano to Macro·J N MockB S Cummings

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Citations

Feb 24, 2007·Pharmacology & Therapeutics·Walter C Prozialeck, Joshua R Edwards
Sep 26, 2006·Biochemical Pharmacology·Maroesja J van Nimwegen, Bob van de Water
Nov 7, 2006·Biochimica Et Biophysica Acta·Stephanie HehlgansNils Cordes
Dec 1, 2009·Biochemical and Biophysical Research Communications·Hyeok-Ran KwonSang-Muk Oh
May 2, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiangxuan ZhaoChen Liu
Jun 27, 2019·Cellular & Molecular Biology Letters·Sichuang TanSipin Tan

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