51177

PLEKHO1

CKIP-1|OC120;pleckstrin homology domain containing, family O member 1;PLEKHO1;pleckstrin homology domain containing, family O member 1

2810052M02Rik|C-Jun-binding protein|CK2 interacting protein 1; HQ0024c protein|CK2-interacting protein 1|JBP|OC120|PH domain-containing family O member 1|casein kinase 2-interacting protein 1|osteoclast maturation-associated gene 120 protein|pleckstrin ho

1q21.2

protein-coding

Count: 2; Generif,UniProt

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.