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Cdk2-dependent phosphorylation of the NF-Y transcription factor and its involvement in the p53-p21 signaling pathway.

Authors
Yun, J; Chae, HD; Choi, TS; Kim, EH; Bang, YJ; Chung, J; Choi, KS; Mantovani, R; Shin, DY
Citation
The Journal of biological chemistry, 278(38):36966-36972, 2003
Journal Title
The Journal of biological chemistry
ISSN
0021-92581083-351X
Abstract
Recent studies have suggested that the NF-Y transcription factor is involved in transcription repression of the cell cycle regulatory genes in a response to p53 induction or DNA damage. Here we demonstrate the cdk2-dependent phosphorylation of NF-Y and its involvement in transcription repression by the p53-p21 signaling pathway. Cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y. Cyclin A-cdk2 appears to associate with NF-Y both in vitro and in vivo. Furthermore, YA protein is phosphorylated in parallel with a cell cycle-dependent activation of cdk2 kinase and cyclin A expression. YA phosphorylation is unnecessary for heterotrimer formation with the YB-YC dimer. However, NF-Y containing a phosphorylation-deficient mutant form of YA, YA-aa, has its DNA binding activity impaired. Consistently, YA-aa inhibits transcription activation of a NF-Y target promoter, cdc2, by cdk2. These results facilitate the elucidation of the regulatory mechanisms of cell cycle progression involving the p21-cdk2-NF-Y signaling pathway.
MeSH terms
Amino Acid SequenceCCAAT-Binding Factor/metabolism*CDC2-CDC28 Kinases/metabolism*Cell CycleCell LineCell Nucleus/metabolismCyclin A/metabolismCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclins/metabolism*DNA DamageDimerizationGlutathione Transferase/metabolismHumansMolecular Sequence DataMutationPhosphorylation*Plasmids/metabolismPrecipitin TestsPromoter Regions, GeneticProtein BindingPurines/pharmacologySerine/chemistrySignal Transduction*Time FactorsTransfectionTumor Suppressor Protein p53/metabolism*
DOI
10.1074/jbc.M305178200
PMID
12857729
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Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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