| RRC ID |
28638
|
| 著者 |
Tokuda E, Fujita N, Oh-hara T, Sato S, Kurata A, Katayama R, Itoh T, Takenawa T, Miyazono K, Tsuruo T.
|
| タイトル |
Casein kinase 2-interacting protein-1, a novel Akt pleckstrin homology domain-interacting protein, down-regulates PI3K/Akt signaling and suppresses tumor growth in vivo.
|
| ジャーナル |
Cancer Res
|
| Abstract |
The serine/threonine kinase Akt plays a central role in cell survival and proliferation. Its activation is linked to tumorigenesis in several human cancers. Although many Akt substrates have been elucidated, the Akt-binding proteins that regulate Akt function remain unclear. We report herein having identified casein kinase 2-interacting protein-1 (CKIP-1) as an Akt pleckstrin homology (PH) domain-binding protein with Akt inhibitory function. CKIP-1 formed a complex with each Akt isoform (Akt1, Akt2, and Akt3) via its NH2 terminus. Dimerization of CKIP-1 via its leucine zipper (LZ) motif at the COOH terminus was found to be associated with Akt inactivation because deletion of the LZ motif eliminated Akt inhibitory function, although it could still bind to Akt. Expression of the NH2 terminus-deleted CKIP-1 mutant containing the LZ motif, but lacking Akt-binding ability, induced Akt phosphorylation and activation by sequestering the ability of endogenous CKIP-1 to bind to Akt. Stable CKIP-1 expression caused Akt inactivation and cell growth inhibition in vitro. In addition, the growth of stable CKIP-1 transfectants xenografted into nude mice was slower than that of mock transfectants. These results indicate that CKIP-1, a novel Akt PH domain-interacting protein, would be a candidate of tumor suppressor with an Akt inhibitory function.
|
| 巻・号 |
67(20)
|
| ページ |
9666-76
|
| 公開日 |
2007-10-15
|
| DOI |
10.1158/0008-5472.CAN-07-1050
|
| PII |
67/20/9666
|
| PMID |
17942896
|
| MeSH |
Amino Acid Sequence
Animals
Binding, Competitive
Carrier Proteins / biosynthesis
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Growth Processes / physiology
Dimerization
Down-Regulation
Female
Humans
Intracellular Signaling Peptides and Proteins
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Neoplasms / genetics
Neoplasms / metabolism*
Neoplasms / pathology*
Phosphatidylinositol 3-Kinases / metabolism*
Phosphatidylinositols / metabolism
Phosphorylation
Protein Binding
Protein Structure, Tertiary
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction
Transfection
|
| IF |
9.727
|
| 引用数 |
44
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pFLAG-CMV-2-WT-human Akt1 (RDB06614)
pFLAG-CMV-2-WT-human Akt2 (RDB06615)
pFLAG-CMV-2-WT-human Akt3 (RDB06616) |
