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.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Carter BZ,Mak DH,Wang Z,Ma W,Mak PY,Andreeff M,Davis RE

doi

10.1016/j.leukres.2013.04.018

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

974-9

issue

8

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(13)00140-9

journal_volume

37

pub_type

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