The transcriptional activity of CITED1 is regulated by phosphorylation in a cell cycle-dependent manner.
CITED1 is the founding member of the CITED family of cofactors that are involved in regulating a wide variety of CBP/p300-dependent transcriptional responses. In the present study, we show that the phosphorylation status of CITED1 changes during the cell cycle and affects its transcriptional cofactor activity. Tryptic mapping and mutagenesis studies identified five phosphorylated serine residues in CITED1. Phosphorylation of these residues did not affect CRM1-dependent nuclear export, but did decrease CITED1 binding to p300 and inhibited CITED1-dependent transactivation of Smad4 and p300. These results suggest that CITED1 functions as a cell cycle-dependent transcriptional cofactor whose activity is regulated by phosphorylation.
Shi
Genbin
G
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2372, and Department of Tumor Biology, Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.
Boyle
Scott C
SC
Sparrow
Duncan B
DB
Dunwoodie
Sally L
SL
Shioda
Toshi
T
de Caestecker
Mark P
MP
D051017:Apoptosis Regulatory Proteins; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D006801:Humans; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051901:Smad4 Protein / Q000737:chemistry*; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014357:Trypsin / Q000737:chemistry / Q000494:pharmacology; D050880:p300-CBP Transcription Factors / Q000737:chemistry*
D051017:Apoptosis Regulatory Proteins; C512688:CITED1 protein, human; D009687:Nuclear Proteins; D051901:Smad4 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D014357:Trypsin