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Title: PH Domain-Only Protein PHLDA3 Is a p53-Regulated Repressor of Akt
Authors: Kawase, T.
Ohki, R.
Shibata, T.
Tsutsumi, S.
Kamimura, N.
Inazawa, J.
Ohta, T.
Ichikawa, H.
Aburatani, H.
Tashiro, F.
Taya, Y. 
Issue Date: 6-Feb-2009
Citation: Kawase, T., Ohki, R., Shibata, T., Tsutsumi, S., Kamimura, N., Inazawa, J., Ohta, T., Ichikawa, H., Aburatani, H., Tashiro, F., Taya, Y. (2009-02-06). PH Domain-Only Protein PHLDA3 Is a p53-Regulated Repressor of Akt. Cell 136 (3) : 535-550. ScholarBank@NUS Repository.
Abstract: p53 and Akt are critical players regulating tumorigenesis with opposite effects: whereas p53 transactivates target genes to exert its function as a tumor suppressor, Akt phosphorylates its substrates and transduces downstream survival signals. In addition, p53 and Akt negatively regulate each other to balance survival and death signals within a cell. We now identify PHLDA3 as a p53 target gene that encodes a PH domain-only protein. We find that PHLDA3 competes with the PH domain of Akt for binding of membrane lipids, thereby inhibiting Akt translocation to the cellular membrane and activation. Ablation of endogenous PHLDA3 results in enhanced Akt activity and decrease of p53-dependent apoptosis. We also demonstrate the suppression of anchorage-independent cell growth by PHLDA3. Loss of the PHLDA3 genomic locus was frequently observed in primary lung cancers, suggesting a role of PHLDA3 in tumor suppression. Our results reveal a new mode of coordination between the p53 and Akt pathways. © 2009 Elsevier Inc. All rights reserved.
Source Title: Cell
ISSN: 00928674
DOI: 10.1016/j.cell.2008.12.002
Appears in Collections:Staff Publications

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