| RRC ID |
42020
|
| 著者 |
Nawata R, Yujiri T, Nakamura Y, Ariyoshi K, Takahashi T, Sato Y, Oka Y, Tanizawa Y.
|
| タイトル |
MEK kinase 1 mediates the antiapoptotic effect of the Bcr-Abl oncogene through NF-kappaB activation.
|
| ジャーナル |
Oncogene
|
| Abstract |
Bcr-Abl tyrosine kinase, a chimeric oncoprotein responsible for chronic myelogenous leukemia, constitutively activates several signal transduction pathways that stimulate cell proliferation and prevent apoptosis in hematopoietic cells. The antiapoptotic function of Bcr-Abl is necessary for hematopoietic transformation, and also contributes to leukemogenesis. Herein, we show for the first time that cell transformation induced by Bcr-Abl leads to increased expression and kinase activity of MEK kinase 1 (MEKK1), which acts upstream of the c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase (ERK) and NF-kappaB signaling pathways. Inhibition of MEKK1 activity using a dominant-negative MEKK1 mutant (MEKK1km) diminished the ability of Bcr-Abl to protect cells from genotoxin-induced apoptosis, but had no effect on the proliferation of Bcr-Abl-transformed cells. Expression of MEKK1km also reduced NF-kappaB activation, and inhibited antiapoptotic c-IAP1 and c-IAP2 mRNA expression in response to the genotoxin. By contrast, neither JNK nor ERK activation was affected. These results indicate that MEKK1 is a downstream target of Bcr-Abl, and that the antiapoptotic effect of Bcr-Abl in chronic myelogenous leukemia cells is mediated via the MEKK1-NF-kappaB pathway.
|
| 巻・号 |
22(49)
|
| ページ |
7774-80
|
| 公開日 |
2003-10-30
|
| DOI |
10.1038/sj.onc.1206901
|
| PII |
1206901
|
| PMID |
14586403
|
| MeSH |
Animals
Apoptosis*
Baculoviral IAP Repeat-Containing 3 Protein
Base Sequence
Cell Line
Genes, abl / physiology*
Inhibitor of Apoptosis Proteins
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
MAP Kinase Kinase Kinase 1*
Mice
Molecular Sequence Data
NF-kappa B / physiology*
Protein Serine-Threonine Kinases / physiology*
Proteins / genetics
RNA, Messenger / analysis
Ubiquitin-Protein Ligases
|
| IF |
7.971
|
| 引用数 |
35
|
|
WOS 分野
|
GENETICS & HEREDITY
ONCOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Ba/F3(RCB0805)
32D(RCB1145) |
