XIAP downregulation promotes caspase-dependent inhibition of proteasome activity in AML cells

Bing Z. Carter; Duncan H. Mak; Zhiqiang Wang; Wencai Ma; Po Yee Mak; Michael Andreeff; R. Eric Davis

doi:10.1016/j.leukres.2013.04.018

XIAP downregulation promotes caspase-dependent inhibition of proteasome activity in AML cells

Bing Z. Carter, Duncan H. Mak, Zhiqiang Wang, Wencai Ma, Po Yee Mak, Michael Andreeff, R. Eric Davis

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

To further understand the role of XIAP in acute myeloid leukemia (AML), we suppressed XIAP expression by antisense oligonucleotides and determined the effect on gene expression profiles and biological pathways. XIAP inhibition upregulated expression of proteasome genes in a manner similar to the proteasome inhibitor bortezomib or MG132; decreased 20S proteasome activity, an effect which was diminished in the presence of a pan-caspase inhibitor; and increased IκBα, Mcl-1, and HSP70 in AML cells. In addition to multiple functions already described, XIAP contributes to increased proteasome activity in AML cells, and the antitumor effect of XIAP inhibition may be mediated in part through caspase-dependent proteasome inhibition.

Original language	English (US)
Pages (from-to)	974-979
Number of pages	6
Journal	Leukemia Research
Volume	37
Issue number	8
DOIs	https://doi.org/10.1016/j.leukres.2013.04.018
State	Published - Aug 2013

Keywords

AML
Caspase
Gene expression
IκBα
Proteasome
XIAP

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility

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10.1016/j.leukres.2013.04.018

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@article{c72f476f0bb14c77bb6a8e7619ddf8b7,

title = "XIAP downregulation promotes caspase-dependent inhibition of proteasome activity in AML cells",

abstract = "To further understand the role of XIAP in acute myeloid leukemia (AML), we suppressed XIAP expression by antisense oligonucleotides and determined the effect on gene expression profiles and biological pathways. XIAP inhibition upregulated expression of proteasome genes in a manner similar to the proteasome inhibitor bortezomib or MG132; decreased 20S proteasome activity, an effect which was diminished in the presence of a pan-caspase inhibitor; and increased IκBα, Mcl-1, and HSP70 in AML cells. In addition to multiple functions already described, XIAP contributes to increased proteasome activity in AML cells, and the antitumor effect of XIAP inhibition may be mediated in part through caspase-dependent proteasome inhibition.",

keywords = "AML, Caspase, Gene expression, IκBα, Proteasome, XIAP",

author = "Carter, {Bing Z.} and Mak, {Duncan H.} and Zhiqiang Wang and Wencai Ma and Mak, {Po Yee} and Michael Andreeff and Davis, {R. Eric}",

note = "Funding Information: This work was supported in part by grants from the National Institutes of Health ( P01 CA055164 and MD Anderson's Cancer Center Support Grant CA016672 ) and by the Paul and Mary Haas Chair in Genetics (M.A) . ",

year = "2013",

month = aug,

doi = "10.1016/j.leukres.2013.04.018",

language = "English (US)",

volume = "37",

pages = "974--979",

journal = "Leukemia Research",

issn = "0145-2126",

publisher = "Elsevier Limited",

number = "8",

}

TY - JOUR

T1 - XIAP downregulation promotes caspase-dependent inhibition of proteasome activity in AML cells

AU - Carter, Bing Z.

AU - Mak, Duncan H.

AU - Wang, Zhiqiang

AU - Ma, Wencai

AU - Mak, Po Yee

AU - Andreeff, Michael

AU - Davis, R. Eric

N1 - Funding Information: This work was supported in part by grants from the National Institutes of Health ( P01 CA055164 and MD Anderson's Cancer Center Support Grant CA016672 ) and by the Paul and Mary Haas Chair in Genetics (M.A) .

PY - 2013/8

Y1 - 2013/8

N2 - To further understand the role of XIAP in acute myeloid leukemia (AML), we suppressed XIAP expression by antisense oligonucleotides and determined the effect on gene expression profiles and biological pathways. XIAP inhibition upregulated expression of proteasome genes in a manner similar to the proteasome inhibitor bortezomib or MG132; decreased 20S proteasome activity, an effect which was diminished in the presence of a pan-caspase inhibitor; and increased IκBα, Mcl-1, and HSP70 in AML cells. In addition to multiple functions already described, XIAP contributes to increased proteasome activity in AML cells, and the antitumor effect of XIAP inhibition may be mediated in part through caspase-dependent proteasome inhibition.

AB - To further understand the role of XIAP in acute myeloid leukemia (AML), we suppressed XIAP expression by antisense oligonucleotides and determined the effect on gene expression profiles and biological pathways. XIAP inhibition upregulated expression of proteasome genes in a manner similar to the proteasome inhibitor bortezomib or MG132; decreased 20S proteasome activity, an effect which was diminished in the presence of a pan-caspase inhibitor; and increased IκBα, Mcl-1, and HSP70 in AML cells. In addition to multiple functions already described, XIAP contributes to increased proteasome activity in AML cells, and the antitumor effect of XIAP inhibition may be mediated in part through caspase-dependent proteasome inhibition.

KW - AML

KW - Caspase

KW - Gene expression

KW - IκBα

KW - Proteasome

KW - XIAP

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U2 - 10.1016/j.leukres.2013.04.018

DO - 10.1016/j.leukres.2013.04.018

M3 - Article

C2 - 23669290

AN - SCOPUS:84879786030

SN - 0145-2126

VL - 37

SP - 974

EP - 979

JO - Leukemia Research

JF - Leukemia Research

IS - 8

ER -

XIAP downregulation promotes caspase-dependent inhibition of proteasome activity in AML cells

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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