Antiapoptotic function of charged multivesicular body protein 5: a potentially relevant gene in acute myeloid leukemia.
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.
Shahmoradgoli
Maria
M
Department of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
Mannherz
Otto
O
Engel
Felix
F
Heck
Stefanie
S
Krämer
Alwin
A
Seiffert
Martina
M
Pscherer
Armin
A
Lichter
Peter
P
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
C499838:CHMP5 protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D020169:Caspases