Prostate-apoptosis-response-gene-4 increases sensitivity to TRAIL-induced apoptosis

Leukemia Research
Simone BoehrerKai Uwe Chow

Abstract

The capacity of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) to preferentially induce apoptosis in malignant cells while sparing normal tissues renders it an attractive therapeutic agent. Nevertheless, the molecular determinants governing sensitivity towards TRAIL remain to be defined. Acknowledging the previously demonstrated deregulation of prostate-apoptosis-response-gene-4 (par-4) in ex vivo cells of patients suffering from acute and chronic lymphatic leukemia, we here tested the hypothesis that expression of par-4 influences sensitivity to TRAIL. Evaluating this hypothesis we show, that par-4-transfected T-lymphoblastic Jurkat cells exhibit a considerably increased rate of apoptosis upon incubation with an agonistic TRAIL-antibody as compared to their mock-transfected counterparts. Defining the underlying molecular mechanisms we provide evidence, that par-4 enhances sensitivity towards TRAIL by employing crucial members of the extrinsic pathway. Thus, par-4-overexpressing Jurkat clones show an enforced cleavage of c-Flip(L) together with an increased activation of the initiator caspases-8 and -10. In addition, expression of par-4 enables cells to down-regulate the inhibitor-of-apoptosis proteins cI...Continue Reading

References

May 31, 1996·The Journal of Biological Chemistry·R M PittiA Ashkenazi
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·J BertinJ I Cohen
Jul 1, 1997·Molecular and Cellular Biology·S F SellsV M Rangnekar
Jun 1, 1997·Immunity·H B ShuD V Goeddel
Jul 25, 1997·The Journal of Biological Chemistry·S M SrinivasulaE S Alnemri
Aug 8, 1997·The Journal of Biological Chemistry·Y V GoltsevD Wallach
Oct 6, 1997·The EMBO Journal·H WalczakC T Rauch
Nov 5, 1997·The Journal of Biological Chemistry·M MacFarlaneE S Alnemri
Feb 21, 1998·Current Biology : CB·P Golstein
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Nov 5, 1999·Biochemical and Biophysical Research Communications·H YamadaS Kawanishi
Apr 27, 2000·Nature Cell Biology·J L BodmerJ Tschopp
May 10, 2000·Nature Medicine·G Kroemer, J C Reed
Feb 24, 2001·Annals of the New York Academy of Sciences·K AbeR Khosravi-Far
Mar 10, 2001·Cold Spring Harbor Symposia on Quantitative Biology·S J KorsmeyerS Zinkel
Oct 5, 2001·The Journal of Biological Chemistry·F C KischkelA Ashkenazi
Nov 20, 2001·Molecular and Cellular Biology·A KruegerS Kirchhoff
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·J WangM J Lenardo
Jul 9, 2002·Apoptosis : an International Journal on Programmed Cell Death·M Chen, J Wang
Sep 11, 2002·Apoptosis : an International Journal on Programmed Cell Death·M Degli Esposti
Mar 20, 2003·The Journal of Biological Chemistry·Sangeeta K CheemaGabriel Lopez-Berestein
Jun 6, 2003·Cytokine & Growth Factor Reviews·Alexandru Almasan, Avi Ashkenazi
Jul 30, 2003·Expert Opinion on Therapeutic Targets·Olivier Micheau
Sep 16, 2003·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Patrizia MariniClaus Belka
Nov 25, 2003·Oncogene·Shulin Wang, Wafik S El-Deiry
Aug 19, 2004·Annals of Hematology·Marion BergmannSimone Boehrer

❮ Previous
Next ❯

Citations

Dec 1, 2006·Apoptosis : an International Journal on Programmed Cell Death·Penny Clarke, Kenneth L Tyler
Apr 7, 2010·Molecular and Cellular Biology·Howard DonningerGeoffrey J Clark
May 11, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Arun K SharmaRosalyn B Irby
Jan 1, 2010·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Simone A de Bessa GarciaMaria A Nagai
Sep 4, 2010·Current Opinion in Cell Biology·Annie YangAvi Ashkenazi
Oct 16, 2012·Expert Opinion on Therapeutic Targets·Rosalyn B Irby, Christina L B Kline
Nov 27, 2018·Current Drug Targets·Renata Virgínia Cavalcanti SantosMichelly Cristiny Pereira

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

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.

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.

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

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.