BAG3 gene silencing sensitizes leukemic cells to Bortezomib-induced apoptosis

被引：58

作者：

Liu, Peng ^{[1
]}

Xu, Bei ^{[2
]}

Li, Jianyong ^{[1
]}

Lu, Hua ^{[1
]}

机构：

[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Hematol, Nanjing, Peoples R China

[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Internal Med, Nanjing, Peoples R China

来源：

FEBS LETTERS | 2009年 / 583卷 / 02期

基金：

中国国家自然科学基金;

关键词：

BAG3; Bortezomib; Leukemia; Apoptosis; Proteasome inhibitor; PROTEASOME INHIBITOR BORTEZOMIB; IN-VIVO; PROTEIN; PATHWAY; CANCER; HSP70/HSC70; SURVIVAL; FAMILY; DEATH; COMPLEX;

D O I：

10.1016/j.febslet.2008.12.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Proteasome inhibition has emerged as a powerful option for the treatment of a number of malignancies including leukemias. However, Bortezomib showed limited single-agent activity for patients with leukemia. Here, we report for the first time that Bortezomib up-regulated a novel antiapoptotic protein, BAG3, in human leukemic cells. BAG3 gene knockdown with shRNA greatly potentiated the generation of apoptosis by Bortezomib in leukemia cells. Furthermore, BAG3 silencing enhanced the antitumor activity of Bortezomib dramatically in a nude mouse model. Our results indicate that knocking down BAG3 gene is a promising new approach to enhance the therapeutic potency of Bortezomib in leukemia. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：401 / 406

页数：6

共 35 条

[1] Proteasome inhibition in cancer: Development of PS-341 [J].

Adams, J .

SEMINARS IN ONCOLOGY, 2001, 28 (06) :613-619

[2]

Adams J, 1999, CANCER RES, V59, P2615

[3] Development of the proteasome inhibitor PS-341 [J].

Adams, J .

ONCOLOGIST, 2002, 7 (01) :9-16

[4] The proteasome: A suitable antineoplastic target [J].

Adams, J .

NATURE REVIEWS CANCER, 2004, 4 (05) :349-360

[5] The development of proteasome inhibitors as anticancer drugs [J].

Adams, J .

CANCER CELL, 2004, 5 (05) :417-421

[6] Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein [J].

Antoku, K ;

Maser, RS ;

Scully, WJ ;

Delach, SM ;

Johnson, DE .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 286 (05) :1003-1010

[7] Staurosporine induces apoptosis through both caspase-dependent and caspase-independent mechanisms [J].

Belmokhtar, CA ;

Hillion, J ;

Ségal-Bendirdjian, E .

ONCOGENE, 2001, 20 (26) :3354-3362

[8] BAG3 protein regulates stress-induced apoptosis in normal and neoplastic leukocytes [J].

Bonelli, P ;

Petrella, A ;

Rosati, A ;

Romano, MF ;

Lerose, R ;

Pagliuca, MG ;

Amelio, T ;

Festa, M ;

Martire, G ;

Venuta, S ;

Turco, MC ;

Leone, A .

LEUKEMIA, 2004, 18 (02) :358-360

[9] The antiapoptotic protein BAG3 is expressed in thyroid carcinomas and modulates apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand [J].

Chiappetta, Gennaro ;

Ammirante, Massimo ;

Basile, Anna ;

Rosati, Alessandra ;

Festa, Michela ;

Monaco, Mario ;

Vuttariello, Emilia ;

Pasquinelli, Rosa ;

Arra, Claudio ;

Zerilli, Monica ;

Todaro, Matilde ;

Stassi, Giorgio ;

Pezzullo, Luciano ;

Gentilella, Antonio ;

Tosco, Alessandra ;

Pascale, Maria ;

Marzullo, Liberato ;

Belisario, Maria Antonietta ;

Turco, Maria Caterina ;

Leone, Arturo .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (03) :1159-1163

[10] THE UBIQUITIN-PROTEASOME PROTEOLYTIC PATHWAY [J].

CIECHANOVER, A .

CELL, 1994, 79 (01) :13-21

← 1 2 3 4 →