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Antiapoptotic function of charged multivesicular body protein 5: A potentially relevant gene in acute myeloid leukemia
Author(s) -
Shahmoradgoli Maria,
Mannherz Otto,
Engel Felix,
Heck Stefanie,
Krämer Alwin,
Seiffert Martina,
Pscherer Armin,
Lichter Peter
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25632
Subject(s) - rna interference , myeloid leukemia , gene silencing , biology , gene , microbiology and biotechnology , apoptosis , leukemia , gene expression , cancer research , function (biology) , rna , genetics
Abstract In recent years, RNA interference (RNAi) has been widely used to uncover gene function or pathway context of novel genes. In our study, we describe a short‐hairpin RNA‐based RNAi screening of a set of functionally uncharacterized human genes for their possible capability to inhibit apoptosis. We thereby identified a new antiapoptotic function for CHMP5 (charged multivesicular body protein 5), which was confirmed by overexpression and rescue assays. Furthermore, caspase assays showed that CHMP5 silencing induced caspase cascade activation mainly through extrinsic apoptosis pathway. Based on genome‐wide expression array profiling, a possible regulatory role of CHMP5 on apoptosis‐associated genes and different signaling pathways including nuclear factor kappa B was revealed. In addition, we found significantly higher CHMP5 mRNA levels in acute myeloid leukemia patients. This observation together with the antiapoptotic feature of CHMP5 suggests a possible oncogenic function for this gene in leukemogenesis.