Chinese Journal of Biochemistry and Molecular Biology. . FoxO1 FoxO1. FoxO1 Transcription Factor and Its Posttranslational Modification

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1 ISSN CN / Q Chinese Journal of Biochemistry and Molecular Biology ~ 208 FoxO1 * FoxO1 Fox DNA / PI-3K Akt FoxO1 FoxO1 FoxO1 FoxO1 DNA FoxO1 FoxO1 FoxO1 FoxO1 FoxO1 Q291 FoxO1 Transcription Factor and Its Posttranslational Modification ZHONG QianDENG Yu-Bin * Department of PathophysiologyZhongshan Medical School Sun Yat-sen UniversityGuangzhou China Abstract As a member of the Fox familyfoxo1 transcription factor is involved in the regulation of apoptosisoxidative stressdna damage repaircancer developmentangiogenesis and glucose metabolism The phosphatidylinositol 3-kinase PI3Kin the Akt pathway phosphorylates FoxO1 and mobilizes FoxO1 from the nuclei to the cytoplasm leading to inactivation of FoxO1 and its impact on the downstream targets Acetylation of FoxO1 attenuates its binding to the target DNA and enhances its phosphorylationthereby decreases the transcription activities of FoxO1 This review focuses on the FoxO1 posttranslational modifications and their roles in the transcriptional regulation Key words FoxO1transcription factorphosphorylationacetylation FoxO1 Fox 2 FoxO1 100 forkhead Fox 1 FoxO1 FoxO Fox FoxO1 FoxO3 FoxO4 1 1 FoxO1 FoxO6 FoxO1 655 N DNA / FoxO Akt /PKB FoxO FoxO1 FoxO1 FoxO1 FoxO1 FoxO1 FoxO1 FoxO * Tel dengyub@ mail sysu edu cn ReceivedJuly 32009AcceptedJunary Supported by National university student innovation test plansun Yat-sen University Yat-sen Innovative Training Program of Sun Yatsen University 2009 * Corresponding author Tel FoxO1 1 FoxOs dengyub@ mail sysu edu cn

2 forkhead FK DNA C / transactivation domainad FoxO1 transrepression domainrd Nuclear Localization SignalNLS Nuclear Export SequenceNES 3 SH3 RD FoxO1 Fig 1 4 Fig 1 The diagram of FoxO1 protein 655 amino acid 4 FoxO1 consists of an N-terminal domain containing a repression domain region RDand a forkhead-domain FKand a C-terminal domain containing a transactivation domain TA FoxO1 contains a nuclear location signal NLSand a nuclear export signal NES The residues that undergo phophorylation by Akt are labeled with P the lysine residues which can be acetylated are labeled with A 1 2 FoxO1 FoxO FoxO1 2Ang Ang-2 Ang-1 FoxO1 FoxO1 Ang Akt /FoxO ephrin -B2 FoxO FoxO1 5 FoxO FoxOs 3 FoxO FoxO1 FoxO3 5 FoxO1 FoxO FoxO3-37 / FoxO1 FoxO3 FoxO4 FoxO1 / + ephrin -B2 65% FoxO3 / FoxO4 / CD4 + CD8 + ephrin -B2 E11 5 Ephrin -B2 FoxO1 12 FoxOs 7 FoxO1 FoxOs 2 FoxOs -1 angiopoietin-1ang-1 FoxOs Ang-1 Akt FoxO1 FoxO1 13

3 3 FoxO FoxO FoxO1 PAX FoxO1 FKHR forkhead in rhabdomyosarcomas FoxO FoxO1 FoxO1 FoxO1 22 t FoxO1 β t113fkhr PAX3 2 β PAX7 FKHR PAX3-FKHR PAX PAX3-FKHR β PAX3-FKHR 1 55% ~ 75% PAX3-FKHR β PAX3 DNA forkhead DNA FKHR PAX3 -FKHR JNK Akt PAX3 FKHR FoxO1 Myf6 pancreatic transcription factor Pdx-1 24 FKHR Pdx 1 β β PAX3-FKHR Ink4a /ARF Trp53 Trp53 Ink4a /ARF β β / PAX3 - FKHR G 1 β ΒIRKO PAX3 - FKHR FoxO1 FoxO1 Pdx-1 PAX3 - FKHR /FoxO1 /Pdx-1 β 2 FoxO1 2 2 FoxO1 FoxO1 PPARγ FoxO1 Thr24 Ser246 Ser256 Ser284 Ser295 Ser319 Ser326 Ser413 Ser415 Ser429 Ser467 Ser475 Thr557 GLUT4 FoxO1 PPARγ PPARγ Asada FoxO1 GLUT4 FoxO1 Ser246 Ser413 Ser415 Ser429 Ser467 FoxO1 PPARγ Ser475 Thr557 1α Pgc1α G6Pase PEPCK FoxO1 Daf-16 /IGF-1 1 / 19 /IGF-1 PI-3K Akt FoxO1 Thr24 Ser256 Ser Fig 1 FoxO FoxO1 β β Glut2 FoxO1 3

4 FoxO1 FoxO1 DNA FoxO1 FoxO1 FoxO1 DNA 30 FoxO FoxO1 3 1 FoxO1 Akt / PKB FoxO1 Ser256 3 FoxOs FoxOs FoxO1 Akt FoxO1 FoxO1 p15ink4bp19ink4d FoxO1 Ser256 p15ink4bp19ink4d FoxO1 CDKI 36 CDK4 CDK Sirt2 3 NAD 31 p27 KIP1 CDK2 FoxO1 p27 KIP1 FoxO1 AKT- Sirt2 Sirt2 CDK2- FoxO1 Sirt2 FoxO1 1 FoxO1 Ser256 FoxO1 FoxO1 PPARγ FoxO1 PPARγ DNA CDK2 CDK2 37 DNA DNA 3 2 FoxO1 CDK2 Sirt1 FoxO1 FoxO1 Ser249 FoxO1 CDK2 1 LXXLL FoxO1 FoxO1 FoxO1 FoxO 3A / PTEN FoxO1 32 LXXAA 3 Akt DNA CDK2 FoxO1 FoxO1 CDK2 IGFBP-1 G6Pase FoxO1 DNA LXXLL FoxO1 Sirt1 33 FoxO1 CDK1 3A /LXXAA FoxO1 Lepr db / db CDK1 FoxO1 Ser249 FoxO FoxO1 Sirt1 FoxO1 34 Huang Sirt1 CDK2 38 CDK FoxO1 3 FoxO1 3T3 -L1 Sirt1 LXXLL G6Pase IGFBP -1 FoxO1 FoxO1 FoxO1 FoxO1 3 Lys242 Lys245 Lys262 CBP FoxO1 Sirt1 Sirt2

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