Differential involvement of Bax and Bak in TRAIL-mediated apoptosis of leukemic T cells

Leukemia
J HanH Rabinowich

Abstract

TRAIL-induced apoptosis has been considered a promising therapeutic approach for tumors that are resistant to chemotherapy, which is usually mediated via mitochondrial apoptotic cascades. Recent studies have shown that in certain cancer cells, TRAIL-mediated apoptosis is also dependent on mitochondrial involvement, suggesting that similar mechanisms of resistance to chemotherapy might be implicated in the resistance of tumor cells to TRAIL. We have used TRAIL-resistant leukemic cells that are deficient in both Bax and Bak to determine the roles of these Bcl-2 members in TRAIL-mediated apoptosis. Exposure of these cells to TRAIL did not have an impact on cell viability, although it induced the processing of caspase-3 to its active p20 subunit. The activity of the p20 caspase-3 appeared to be inhibited as no autoprocessing of this p20 subunit or cleavage of known caspase-3 substrates were detected. Also, in the absence of Bax and Bak, no release of mitochondrial apoptogenic proteins was observed following TRAIL treatment. Adenoviral transduction of the Bax, but not the Bak gene, to the Bax/Bak-deficient leukemic cells rendered them TRAIL-sensitive as assessed by enhanced apoptotic death and caspase-3 processing. These findings de...Continue Reading

References

Aug 28, 1998·Science·A Ashkenazi, V M Dixit
Apr 21, 1999·Current Opinion in Cell Biology·A Ashkenazi, V M Dixit
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Jul 31, 1999·The Journal of Biological Chemistry·C ScaffidiM E Peter
Mar 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·B Li, Q P Dou
Nov 4, 2000·Science·L ZhangB Vogelstein
Nov 21, 2000·The Journal of Experimental Medicine·J A HeibeinR C Bleackley
Mar 30, 2001·The Journal of Biological Chemistry·N KeJ C Reed
Apr 3, 2001·Nature Medicine·D LawrenceA Ashkenazi
Jul 12, 2001·The Journal of Biological Chemistry·G Q WangH Rabinowich
Oct 5, 2001·The Journal of Biological Chemistry·F C KischkelA Ashkenazi
Nov 7, 2001·The Journal of Experimental Medicine·G Q WangH Rabinowich
Jan 10, 2002·Genes & Development·Yibin DengXiangwei Wu
Jan 22, 2002·The Journal of Biological Chemistry·Domagoj VucicVishva M Dixit
Feb 28, 2002·Apoptosis : an International Journal on Programmed Cell Death·A M Verhagen, D L Vaux
Apr 12, 2002·Oncogene·Simone FuldaKlaus-Michael Debatin
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·Guy S Salvesen, Colin S Duckett
Sep 10, 2002·The Journal of Biological Chemistry·Christina R ArntScott H Kaufmann
Mar 7, 2003·Molecular Cell·Kelly M BoatrightGuy S Salvesen
Mar 7, 2003·Molecular Cell·Mrudula DonepudiMarkus G Grütter
Jul 26, 2003·Science·Emily H Y ChengStanley J Korsmeyer

❮ Previous
Next ❯

Citations

Sep 5, 2006·Apoptosis : an International Journal on Programmed Cell Death·Ozgur Kutuk, Huveyda Basaga
Mar 11, 2010·Apoptosis : an International Journal on Programmed Cell Death·Lubomir ProchazkaJiri Neuzil
Nov 28, 2012·Apoptosis : an International Journal on Programmed Cell Death·Syam Prakash SomasekharanJean-Claude Martinou
Dec 23, 2006·Cell Death and Differentiation·U SivaprasadA Basu
Sep 10, 2004·Leukemia·O Micheau, D Mérino
Aug 5, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xing DuIra Pastan
Apr 13, 2012·EMBO Molecular Medicine·Luigi LeanzaIldikò Szabò
Feb 27, 2009·Expert Opinion on Investigational Drugs·Patricia Moretto, Sébastien J Hotte
Jan 26, 2011·Cancer Biology & Therapy·Hope M AmmDonald J Buchsbaum
Apr 10, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas F Gajewski
Oct 7, 2006·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Mário L de Lemos
Nov 24, 2006·Journal of Dental Research·A JewettN A Cacalano
Feb 16, 2006·The Journal of Biological Chemistry·Jie HanHannah Rabinowich

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.